Successful treatment of herpes labialis with topical acyclovir.

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.     

Failure of acyclovir cream in treatment of recurrent herpes labialis.

A double blind, randomised, crossover placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 45 patients with recurrent herpes labialis. These patients had a total of 72 episodes, 34 of which were treated with the 5% acyclovir cream and 38 with placebo cream. Treatment was begun by the patients as soon as possible after the onset of prodromal symptoms. There was no significant clinical benefit from treatment with acyclovir cream compared with placebo cream. The median healing times were nine days with acyclovir cream, 10 days with placebo cream, and 13 days when no treatment was given. The possibility that the 40% propylene glycol cream base alone has a therapeutic effect must therefore be considered.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised,double blind,placebo controlled trial.

OBJECTIVES--To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN--Randomised, double blind, placebo controlled trial. SUBJECTS--74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES--Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS--The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION--Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.

A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10 fixed combination, Kan Jang, in the treatment of acute upper respiratory tract infections, including sinusitis. Ninety-five individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. The medication was taken for 5 days. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the verum group versus the placebo. This result applied to the group as a whole and to the sinusitis subgroups. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduced in the verum group. It can be concluded that Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.     

Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial.

This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee. The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective. In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (p<0.001). The significance is confirmed through the evaluation of the diary, the VCAS evaluation and the separate assessment of the two centres. This also applies to the separate assessment of the VAS total score following pain at rest and on movement. The WOMAC (Western Ontario and McMaster Universities) total score (secondary target value) also improved similar to the VAS total score. At the end of the trial, a reduction by 60.4 mm (58.0%) was recorded for the verum group and a reduction of 14.7 mm (14.1%) for the placebo group. The average group difference of 45.7 mm (95% confidence interval=37.1 to 54.3 mm) or 43.9% is significant (p<0.001). The difference between the treatment groups increased systematically and significantly, in parallel with the duration of the treatment. Thus, the superiority of the treatment with Kytta-Salbe f over that with the placebo is proven, even by means of the multi-factorial multivariate analysis for repetitive measurements. In respect of the explorative secondary target values SF-36 (quality of life), angle measurement (mobility of the knee), CGI (clinical global impression) and global assessment of efficacy by the physician and the patient, a significant superiority (p<0.001 each) of the verum group over the placebo group was also proven. The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.     

Efficacy and safety of foscarnet for recurrent orolabial herpes: a multicentre randomized double-blind study.

Foscarnet sodium (trisodium phosphonoformate hexahydrate) has been shown to inhibit herpes simplex virus (HSV) in vitro and to be efficacious for topical treatment of experimental HSV infection in animals. To assess its clinical efficacy in the treatment of recurrent orolabial herpes a multicentre collaborative, double-blind, placebo-controlled trial was conducted. The study patients were randomly assigned to receive either 3% foscarnet cream (78 patients) or placebo (cream vehicle) (75 patients) and were asked to start treatment at the earliest indication of a recurrence. Efficacy was evaluated in 143 patients (74 in the foscarnet group and 69 in the placebo group). There was no significant difference in time to healing or duration of virus shedding between the two groups. However, in the subgroup of patients who started treatment before vesicles appeared, the duration of virus shedding was shorter in the foscarnet group than in the placebo group (p = 0.04), and the proportion of lesions that evolved to the vesicular stage was smaller (p = 0.03). No significant difference in the incidence of local or systemic adverse effects was noted between the two groups. We conclude that the beneficial effect of foscarnet was limited to a subgroup of patients who started treatment in the prevesicular stage.     

Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection.

Two randomized double-blind, placebo-controlled parallel group clinical trials were performed to investigate the effect of a standardized extract (SHA-10) of Andrographis paniculata fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infections. 46 patients in the pilot study and 179 patients in the phase III study completed the study according to the protocol. Medication was taken three times daily for a minimum of 3 days and a maximum of 8 days for the pilot study, and for exactly three days in the phase III study. The primary outcome measures in the patients self-evaluation were: related to pain in the muscle, cough, throat symptoms, headache, nasal symptoms and eye symptoms and temperature. The physician's fixed score diagnosis was based mainly on sign/symptoms: ears, nose, oral cavity, lymph glands-tonsils and eyes. The total symptom score showed a tendency toward improvement in the pilot study (p = 0,08), while both the total symptom score and total diagnosis score showed highly significant improvement (p < or = 0.0006 resp. 0.003) in the verum group as compared with the placebo. In both studies throat symptoms/signs, were found to show the most significant improvement.     

Clinical Evaluation of Kethoxal Against Cutaneous Herpes Simplex

A 2.5% preparation of kethoxal in cream was compared with the cream placebo for efficacy against cutaneous herpes simplex in a double-blind clinical study. The kethoxal formulation was not significantly more effective than the placebo. This conclusion was based on subjective impressions of the patients, observations by the physicians, and quantitative measurement of herpesvirus recovered from the lesions. It was suggested that the lack of clinical activity, in contrast to the marked activity against experimental infections in laboratory animals, resulted from the fact that high levels of herpesvirus were already present in the skin before symptoms were noted.     

Direct lymphocytotoxicity against herpes simplex virus infected cells.

This study was undertaken to determine if direct cytotoxicity (DC) against herpes simplex virus infected cells, perhaps mediated by T cells, could be demonstrated in individuals subject to recurrent herpes labialis. The mononuclear cells from 7 out of 17 individuals with recurrent herpes expressed DC whereas no DC was ever exhibited by 7 individuals without a previous history of herpes infections. Several approaches were used to show that the cytotoxicity being detected was predominately of the direct type rather than antibody-dependent cell cytotoxicity (ADCC). Since the effector cells of the DC were sensitive to trypsin treatment and behaved as do natural killer (NK) cells upon cell fractionation, the results were taken to imply that the DC was attributable to a NK-effector cell type rather than a classical T lymphocyte.     

gamma Interferon production appears to predict time of recurrence of herpes labialis

Peripheral blood mononuclear cells separated from the blood of 29 volunteers within 3 wk of the onset of recurrent oral herpes labialis spontaneously secreted IFN-gamma (and small amounts of IFN-beta) into the culture medium in varying amounts (mean = 77 U/ml, SE = 17). However, interferon could not be detected in the serum of 10 of these patients tested. In the group as a whole, peak levels of interferon were secreted in vitro at 6 to 20 days after the onset of herpes labialis. Serial studies in eight patients showed peak production in the second or third week, with subsequent decrease to undetectable levels at 6 wk. A strong correlation between peak supernatant interferon level and the time to the next recurrence of herpes labialis in each patient was noted (r = 0.82, p less than 0.0001). Herpes simplex antigen-stimulated mononuclear cell cultures from each patient produced a mixture of IFN-alpha and IFN-gamma. A less marked but still significant correlation was noted between the peak mixed interferon level and the inter-recurrence interval (r = 0.52, p less than 0.005). These results suggest that a recurrent herpes labialis acts as an in vivo stimulus to the induction of IFN-gamma-producing cells that circulate in peripheral blood. The IFN-gamma produced is either a direct determinant of frequency of recurrence of herpes or a quantitative marker for other cellular immune events determining frequency.     

Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial

Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm³ were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm³ or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation.     

Clinical trials with hypericum extracts in patients with depression--results, comparisons, conclusions for therapy with antidepressant drugs.

By the spring of 2002, results from 34 controlled, double-blind trials of Hypericum extracts in some 3000 patients, predominantly with mild to moderate forms of depression, had been published. An overview is given of the studies conducted since 1990. In the majority of them, the efficacy criterion (primary endpoint) was the score and/or response rate on the Hamilton Rating Scale of Depression (HAMD). In ten studies, based on extracts prepared with 50% or 60% ethanol in water (V/V), the dosages ranged from 300 mg to 1050 mg of extract per day. Five of the ten studies were placebo-controlled and in all five cases, the Hypericum extract was shown to be significantly superior. Results with Hypericum were as good or even better than with imipramine or fluoxetine. In the period since 1990, a total of twelve controlled trials have been published with one particular extract prepared with 80% methanol in water (V/V), of which six were placebo-controlled, two compared Hypericum with imipramine and one each with maprotiline, amitriptyline, sertraline or light therapy. Dosages ranged from 450-1200 mg extract per day. Statistical analysis of the total Hamilton scores showed significant differences between Hypericum extract and placebo in four of the six placebo-controlled studies and a trend in favour of the active treatment in the other two. Of the five comparative trials against four different synthetic antidepressants, amitriptyline was significantly superior to Hypericum after six weeks of therapy, whilst there were no significant differences in treatment outcome between Hypericum and the other synthetics in the remaining four studies. The results of the trials conducted to date show no major differences in efficacy of the alcoholic extracts. Taking all the results into account, it can be assumed that the threshold dose for efficacy against individual symptoms and complaints that occur in the course of the depressive illness could be about 300 mg of extract per day. In the medically supervised treatment of mild to moderate depression, doses of approximately 500-1000 mg of extract per day of these preparations of St. John's Wort are of comparable efficacy to synthetic antidepressants in their normally prescribed dosages.     

Antihirsutism activity of Fennel (fruits of Foeniculum vulgare) extract. A double-blind placebo controlled study.

Idiopathic hirsutism is defined as the occurrence of excessive male pattern hair growth in women who have a normal ovulatory menstrual cycle and normal levels of serum androgens. It may be a disorder of peripheral androgen metabolism. In this study we evaluated the clinical response of idiopathic hirsutism to topical Fennel extract. Fennel, Foeniculum vulgare, is a plant, which has been used as an estrogenic agent. The ethanolic extract of Fennel was obtained by using a soxhlete apparatus. In a double blind study, 38 patients were treated with creams containing 1%, 2% of Fennel extract and placebo. Hair diameter was measured and rate of growth was considered. The efficacy of treatment with the cream containing 2% Fennel is better than the cream containing 1% Fennel and these two were more potent than placebo. The mean values of hair diameter reduction was 7.8%, 18.3% and -0.5% for patients receiving the creams containing 1%, 2% and 0% (placebo) respectively.     

Effects of treatment with a cetylated fatty acid topical cream on static postural stability and plantar pressure distribution in patients with knee osteoarthritis

The purpose of the present investigation was to examine the effects of 30 days of treatment with a topical cream consisting of cetylated fatty acids on static postural stability and plantar pressures in patients with osteoarthritis (OA) of one or both knees. Forty patients diagnosed with knee OA were randomly assigned to 1 of 2 topical treatment groups: (a) cetylated fatty acid (CFA; N = 20; age = 62.7 +/- 11.7 years); or (b) placebo (P; N = 20; age = 64.6 +/- 10.5 years). Patients were tested on 2 occasions: (a) baseline (T1), and (b) following a 30-day treatment period consisting of cream application twice per day (T2). Assessments included 20- and 40-second quiet standing protocols on a force plate to measure center of pressure (COP) total excursion length, COP velocity, and rearfoot and forefoot plantar pressure distribution. In the CFA group, a significant reduction in the COP excursion length and velocity were observed at T2, whereas no significant differences were observed in the P group. No significant differences in mean forefoot, rearfoot, or rearfoot-to-forefoot plantar pressure ratios were observed in either group at T2. However, in a subgroup of participants designated to be right- or left-side dominant, improvements in the right-to-left forefoot plantar pressure ratios were observed in both groups. These data indicate that 30 days of treatment with a topical cream consisting of cetylated fatty acids improves static postural stability in patients with knee OA presumably due to pain relief during quiet standing. Such over-the-counter treatment may help improve the exercise trainability of people with OA.     

Biochemical and clinical effects of an antioxidative supplementation of geriatric patients

Ninety seven geriatric patients from two Danish homes for old people accepted to participate in a blinded experiment designed to counteract ageing phenomena. The subjects were split into two groups, i.e., the verum and the placebo group. The verum group received daily for one year an antioxidative cocktail consisting of: 300 micrograms selenium as L-selenomethionine, 45 mg zinc, 270 mg vitamin C, 2.7 mg vitamin A, 6 mg vitamin B-6, and 465 mg vitamin E (d-alfatocopherol). Furthermore, in order to enhance exchange in polyenoic acids, each subject received daily 250 mg gamma-linolenic acid. The placebo groups received similar looking pills and capsules without the active components. During one year in the verum group, the whole blood selenium, the hydrogen-dependent glutathione peroxidase (GSH-Px) of erythrocytes, and the vitamin E level in serum was found increased compared to the pretreatment values and to the placebo group. No change could be traced in the t-butylhydroperoxide dependent GSH-Px, an enzyme that also assays the glutathione-s-transferase. During the same period of time, the fasting levels of serum fatty acids and the content of lipofuscin in erythrocytes were estimated. Compared to the pretreatment values, the lipofuscin level declined significantly and the level of w-3 penta- and hexaenoic acids increased in the verum, but not in the placebo group. During the study period, slight, but significant improvements in psychological scores could be traced. Furthermore, the assays of bloodflow in different areas of the brain surface (i.e., the ISI values) revealed a general trend to improvement in all areas, when the ISI values were compared during treatment with the pretreatment values and the values in the placebo group.     

Human neutrophil--mediated destruction of antibody sensitized herpes simplex virus type I infected cells

Human peripheral blood polymorphonuclear neutrophils (PMN) were tested for their ability to act as effector cells in antibody-dependent cell cytotoxicity (ADCC) against Herpes simplex virus (HSV) infected target cells sensitized with anti-HSV serum. The PMN from all 29 individuals tested could mediate ADCC in the presence of a standard human anit-HSV serum. Since PMN are prominent cells early in herpes lesions, it was hypothesized that because ADCC could represent an in vitro model for antiviral recovery, perhaps the efficacy of PMN at mediating ADCC might be impaired in those subjects to frequent recrudescent herpes. However, evidence for the hypothesis was not obtained since the PMN from individuals with frequent, infrequent, or unrecorded herpes labialis all showed approximately the same activity at mediating ADCC. Alternative ways in which PMN could be involved in antiviral recovery were discussed.     

Thermal Resistance of Certain Oncogenic Viruses Suspended in Milk and Milk Products

Thermal destruction rate curves were determined for adenovirus 12, reovirus 1, and herpes simplex virus in sterile milk, raw milk, raw chocolate milk, and raw ice cream mix. At 40 to 60 C, the curves were asymptotic to the base line. At 65 C, which is near the pasteurization standard, the curves approached a first-order reaction. Thermal resistance studies, by means of in vivo assays, of Moloney and Rauscher leukemia viruses and Moloney and Rous sarcoma viruses indicated that Rous sarcoma was the most resistant. A comparison of the 12D processes of Rous sarcoma virus, reovirus 1, adenovirus 12, and herpes simplex virus in ice cream mix (the most protective of the suspending menstrua studied) with the U.S. Public Health Service pasteurization standard indicated an adequate safety factor in current pasteurization practices.     

Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults

Reactivation of latent herpes virus has been linked to triggers of mild immunosupression, such as stress or UV-exposure. Despite having predictive value in severe immunodeficiency, the white blood cell (WBC) differential count has not been examined in relation to risk of herpes reactivation in population studies. The WBC differential count and other risk factors for herpes labialis were examined in 5687 adults (ages 18-64) from the Third National Health and Nutrition Examination Survey, who had WBC 3.5-11 x 10(6) cells mL(-1) and reported no acute infections in the past month. The association between self-reported herpes labialis in the past year and the WBC differential count was modeled, adjusting for age, sex, race/ethnicity, education, smoking, upper respiratory infections (URI), and HSV-1 antibodies. Herpes labialis was significantly associated with white race/ethnicity, being a nonsmoker, and frequent URI. Compared with the highest quartile, being in the lowest quartile of granulocytes was associated with herpes labialis, adjusted odds ratio=1.82 (95% confidence interval 1.20, 2.28). At the same time, there was a trend towards an inverse association of lower lymphocyte count and herpes labialis. These findings suggest that moderate differences in the WBC differential count are related to reactivation of HSV-1. Prospective studies may help to show whether such differences indicate susceptibility to loss of latency or represent a consequence of reactivated infection.     

Efficacy and tolerability of potato juice in dyspeptic patients: a pilot study.

In Europe, use of potatoes (Solani tuberosi tuberecens) is a traditional remedy for stomach complaints. We performed a pilot study on the effectiveness and tolerability of freshly squeezed potato juice in patients suffering from dyspeptic symptoms. After informed written consent, 44 patients with various dyspeptic symptoms were enrolled, to drink for 1 week twice daily 100ml or more of potato juice (Biotta, if complaints persisted, a further 100ml was recommended. Validated outcome measures included the gastrointestinal symptom (GIS) profile, a disease-specific health assessment questionnaire (QOLRAD) and self-rated treatment success (efficacy, a 5-point Likert Scale). The study was completed by 42 patients. The GIS and QOLRAD scores improved significantly by 41.9+/-40.8% (p=0.001) and 50.7+/-36.1% (p<0.001), respectively (ITT); the absolute values changed from 11.5+/-5.1 to 6.3+/-5.3 (GIS) and 62.0+/-25.7 to 32.0+/-28.8 (QORAD). Sixteen, 18 and 26 patients, respectively, rated the effectiveness of the treatment as very good or good on the GIS, QOLRAD (improvements >60%) and on efficacy, respectively. Poor treatment success was achieved in 13 (GIS), 11 (QOLRAD) and 10 (Efficacy), not necessarily by the same patients. Since about two-thirds of the patients benefited to some extent from the treatment, potato juice in its present formulation may be useful for self-treatment. However, placebo-controlled studies with a longer treatment period are needed to confirm this.     

Interleukin-12 exhibits potent antiviral activity in experimental herpesvirus infections.

The prophylactic and therapeutic efficacy of interleukin-12 was studied by using murine models of herpes simplex virus infection. Prophylactic administration consisted of two intraperitoneal doses of interleukin-12 given 48 and 24 h prior to infection. Therapeutic intraperitoneal administration of interleukin-12 commenced 6 h after the mice were infected with herpes simplex virus and was continued daily for a total of 5 days. Interleukin-12 therapy improved the survival rates of mice with systemic herpes simplex virus infection compared with those of placebo-treated infected mice. Subcutaneous administration of interleukin-12 also improved the rate of survival of mice after systemic herpes simplex virus infection, although higher doses were required to give comparable effects. Combined prophylactic and therapeutic administration of interleukin-12 produced the greatest effect on survival after an otherwise lethal systemic infection. Intraperitoneal administration of interleukin-12 for 2 days before and 3 days after systemic infection with herpes simplex virus resulted in survival of 80% of the mice. These surviving mice were resistant to subsequent reinfection with herpes simplex virus. Such resistance was apparently specific for herpes simplex virus infection, since a second group of survivors succumbed to a lethal infection with murine cytomegalovirus. Infectious virus was recovered from lumbar ganglia explants dissected from survivors of prophylactic interleukin-12 therapy and cultured for 5 days in vitro, suggesting that interleukin-12 treatment did not prevent the establishment of latent herpes simplex virus infection. One action of interleukin-12 may be to enhance natural killer cell-mediated clearance of the virus. However, interleukin-12 therapy was also effective in mice carrying the beige mutation, which reduces natural killer cell lytic activity, suggesting that interleukin-12 has additional activities in vivo.