Early life experiences affect adult delayed-type hypersensitivity in short and long photoperiods

Environmental experiences during development provide animals with important information about future conditions. Siberian hamsters are photoperiodic rodents that dramatically adjust their physiology and behavior to adapt to seasonal changes. For example, during short winter-like days, hamsters enhance some components of immune function putatively to cope with increasing environmental challenges. Furthermore, early life stress alters the developmental course of the immune system. Overall, immune function is typically suppressed in response to chronic stress, but responses vary depending on the type of stress and components of immune function assessed. This led us to hypothesize that delayed-type hypersensitivity (DTH), an antigen-specific, cell-mediated immune response, would be differentially modulated in hamsters that underwent early life maternal separation (MS) in either short or long photoperiods. At birth, hamsters were assigned to either short (SD; 8 h light/day) or long (LD; 16 h light/day) photoperiods and either daily 3 h MS, daily 15-min brief maternal separation (BMS), or no manipulation from postnatal day 2 through 14. In adulthood DTH was assessed. Hamsters reared in short days enhanced DTH responses. MS and BMS attenuated DTH responses in both short and long days. However, BMS long-day female hamsters did not suppress pinna swelling, suggesting a protective effect of female sex steroids on immune function. As is typical in short days, reproductive tissue was regressed. Reproductive tissue mass was also decreased in long-day MS female hamsters. Furthermore, MS altered photoperiod-induced changes in body mass. Taken together, these findings suggest that manipulations of early life mother-pup interactions in Siberian hamsters result in physiological changes and suppressed cell-mediated immunity.     

Experimental Mycoplasma pulmonis infection of rats suppresses humoral but not cellular immune response

Humoral antibody response to sheep red blood cells and cellular immune response to bovine serum albumin were studied in Mycoplasma pulmonis infected, adult, male Sprague-Dawley rats. The hemagglutinating antibody response to sheep red blood cells was evaluated at 0, 3, 5, 7, 14, 21 and 28 days postinfection. Antibody titers during all days postinfection were depressed significantly (p less than 0.05) in infected rats as compared to noninfected controls. Cellular immune responses were evaluated by a delayed hypersensitivity response. Rats were sensitized at 0, 3, 5, 7, 14, 21 or 28 days postinfection with bovine serum albumin and challenged with heat aggregated bovine serum albumin 7 days later. Cell-mediated immune responses in infected rats were not significantly different at any point from controls. These results indicate that M. pulmonis infection in rats suppresses the humoral antibody response to sheep red blood cells, but not the cellular immune response to bovine serum albumin.     

Early Life Experiences Affect Adult Delayed-Type Hypersensitivity in Short and Long Photoperiods

Environmental experiences during development provide animals with important information about future conditions. Siberian hamsters are photoperiodic rodents that dramatically adjust their physiology and behavior to adapt to seasonal changes. For example, during short winter-like days, hamsters enhance some components of immune function putatively to cope with increasing environmental challenges. Furthermore, early life stress alters the developmental course of the immune system. Overall, immune function is typically suppressed in response to chronic stress, but responses vary depending on the type of stress and components of immune function assessed. This led us to hypothesize that delayed-type hypersensitivity (DTH), an antigen-specific, cell-mediated immune response, would be differentially modulated in hamsters that underwent early life maternal separation (MS) in either short or long photoperiods. At birth, hamsters were assigned to either short (SD; 8?h light/day) or long (LD; 16?h light/day) photoperiods and either daily 3?h MS, daily 15-min brief maternal separation (BMS), or no manipulation from postnatal day 2 through 14. In adulthood DTH was assessed. Hamsters reared in short days enhanced DTH responses. MS and BMS attenuated DTH responses in both short and long days. However, BMS long-day female hamsters did not suppress pinna swelling, suggesting a protective effect of female sex steroids on immune function. As is typical in short days, reproductive tissue was regressed. Reproductive tissue mass was also decreased in long-day MS female hamsters. Furthermore, MS altered photoperiod-induced changes in body mass. Taken together, these findings suggest that manipulations of early life mother-pup interactions in Siberian hamsters result in physiological changes and suppressed cell-mediated immunity. (Author correspondence: fonken.1@osu.edu).     

Immune response to chemically modified flagellin. IV. Further studies on the relationship between humoral and cell-mediated immunity

Acetoacetylation converts flagellin from an antigen which preferentially induces humoral antibodies to an antigen which exclusively provokes cell-mediated immunity and, under certain circumstances, induces antibody tolerance. Studies reported in this paper revealed that the acetoacetylated flagellins expressed similar immunological properties in flagellin primed rats as in normal rats. Thus, on the one hand, acetoacetylation destroyed the capacity of flagellin to trigger a secondary antibody response, but on the other hand, the acetoacetyl-flagellins very effectively induced delayed-type hypersensitivity reactions in flagellin primed animals. It was concluded from these results that humoral and cell-mediated immunity may be opposing immunological processes in both unprimed and primed animals.Acetoacetylated flagellin induced antibody tolerance in both strain W (low responder) and J (high responder) Wistar rats. Maximum tolerance was induced 12 hr after injection of antigen, but in strain J animals the tolerance had disappeared by 48 hr, whereas in strain W rats tolerance persisted for >28 days. The potential to recover from tolerance in strain J rats appeared to coincide with the level of delayed hypersensitivity at the time of challenge. However, this delayed hypersensitivity disappeared when breaking of tolerance occurred. These results suggest that the T cells which participate in delayed hypersensitivity reactions may also act as “helper” cells in antibody responses. On the other hand, it was found that priming for a secondary antibody response by flagellin appeared to coincide with development of primary antibodies rather than with induction of delayed-type hypersensitivity. The relative importance of specific T and B cells in these phenomena is discussed.     

Immune responses to vaginal or systemic infection of BALB/c mice with herpes simplex virus type 2.

The temporal relationships among the humoral and cellular immune responses were defined in BALB/c mice after vaginal or systemic infection with herpes simplex virus type 2 (HSV-2). After vaginal infection, mice showed evidence of clinical vaginitis on days 4 to 6 and HSV-2 replication was detected locally in the vaginal secretions, cervix, vagina, and uterus before the virus subsequently spread to the central nervous system. Death from encephalitis occurred between 7 and 10 days after infection. Vaginal infection was associated with significant delayed type hypersensitivity and splenic proliferative cell-mediated immune responses which appeared during the acute infection and waned by 3 weeks. There was almost no evidence of a systemic neutralizing antibody response at any time after vaginal infection. In contrast to the local vaginal infection, systemic i.v. HSV-2 infection induced a humoral response as well as the two cellular immune responses. Although both cellular immune responses appeared during the acute infection (days 6 to 14) and persisted for approximately 5 weeks, the humoral response appeared in surviving animals and persisted for at least 4 months. Thus, vaginal HSV-2 infection was associated primarily with transient cellular immune responses, whereas i.v. HSV-2 infection induced prolonged systemic humoral and cellular immune responses.     

DNA vaccines for influenza virus: differential effects of maternal antibody on immune responses to hemagglutinin and nucleoprotein

Maternal antibody is the major form of protection from disease in early life when the neonatal immune system is still immature; however, the presence of maternal antibody also interferes with active immunization, placing infants at risk for severe bacterial and viral infection. We tested the ability of intramuscular and gene gun immunization with DNA expressing influenza virus hemagglutinin (HA) and nucleoprotein (NP) to raise protective humoral and cellular responses in the presence or absence of maternal antibody. Neonatal mice born to influenza virus-immune mothers raised full antibody responses to NP but failed to generate antibody responses to HA. In contrast, the presence of maternal antibody did not affect the generation of long-lived CD8(+) T-cell responses to both HA and NP. Thus, maternal antibody did not affect cell-mediated responses but did affect humoral responses, with the ability to limit the antibody response correlating with whether the DNA-expressed immunogen was localized in the plasma membrane or within the cell.     

Trikatu,an herbal compound as immunomodulatory and anti-inflammatory agent in the treatment of rheumatoid arthritis – An experimental study

In the present study, trikatu, an herbal compound was evaluated for its immunomodulatory and anti-inflammatory properties with reference to cell mediated immune responses (delayed type hypersensitivity reaction), humoral immune response (haemagglutination titer and plaque forming assay), macrophage phagocytic index, circulating immune complex and inflammatory mediators in rats. For comparison purposes, indomethacin was used as a reference drug for anti-inflammatory studies. The results obtained in our study showed a significant decrease in cell mediated immune responses, humoral immune responses (haemagglutination titre and plaque forming assay) and macrophage phagocytic index in trikatu treated rats (1000 mg/kg/b.wt.) compared to control animals implying its immunosuppressive property. In addition, significant anti-inflammatory effects were observed in trikatu treated adjuvant induced arthritic rats by a reduction in the levels of circulating immune complexes and inflammatory mediators (TNF-alpha and Interleukin-1beta). Thus, in conclusion, our data suggest that trikatu could be considered as a potential anti-inflammatory agent for treating autoimmune inflammatory disorders like rheumatoid arthritis with immunosuppressive property.     

Dim light at night increases immune function in Nile grass rats, a diurnal rodent

With the widespread adoption of electrical lighting during the 20th century, human and nonhuman animals became exposed to high levels of light at night for the first time in evolutionary history. This divergence from the natural environment may have significant implications for certain ecological niches because of the important influence light exerts on the circadian system. For example, circadian disruption and nighttime light exposure are linked to changes in immune function. The majority of studies investigating the effects of light exposure and circadian disruption on the immune system use nocturnal rodents. In diurnal species, many hormones and immune parameters vary with secretion patterns 180° out of phase to those of nocturnal rodents. Thus, the authors investigated the effects of nighttime light exposure on immunocompetence in diurnal Nile grass rats (Arvicanthis niloticus). Rats were housed in either standard 14-h light (L):10-h dark (D) cycles with L ～150 lux and D 0 lux or dim light at night (dLAN) cycles of LD 14:10 with L ～150 lux and D 5 lux for 3 wks, then tested for plasma bactericidal capacity, as well as humoral and cell-mediated immune responses. Rats exposed to dLAN showed increased delayed-type hypersensitivity pinna swelling, which is consistent with enhanced cell-mediated immune function. dLAN rats similarly showed increased antibody production following inoculation with keyhole lymphocyte hemocyanin (KLH) and increased bactericidal capacity. Daytime corticosterone concentrations were elevated in grass rats exposed to nighttime dim light, which may have influenced immunological measures. Overall, these results indicate nighttime light affects immune parameters in a diurnal rodent.     

Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats

In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. The aims of this study were 1) to determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity as well as on other measures of stress sensitivity of the adult animal; and 2) to determine the role of corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF(1)R) in mediating visceral hypersensitivity. Three groups of male Long-Evans rat pups were used: separation from their dam for 180 min daily from postnatal days 2-14 (MS180), daily separation (handling) for 15 min (H), or no handling. The visceromotor responses (VMR) to colorectal distension, stress-induced colonic motility, and anxiety-like behavior were assessed in the adult rats. The VMR was assessed at baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h poststress. Astressin B, a nonselective CRF-R antagonist, or CP-154,526, a selective CRF(1)R antagonist, was administered before the stressor and/or before the 24-h measurement. MS rats developed acute and delayed stress-induced visceral hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited enhanced stress-induced colonic motility and increased anxiety-like behavior. In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF(1)R system.     

Immunotoxicity of phosphamidon following subchronic exposure in albino rats

Effect of subchronic doses of phosphamidon exposure on humoral and cell mediated immune (CMI) responses were studied in male albino rats using SRBC, ovalbumin and KLH as antigens. Humoral immune responses were assessed by estimating antibody titre against antigen and splenic plaque forming cells (PFC) assay. CMI responses were studied by using leucocyte migration inhibition (LMI), macrophage migration inhibition (MMI) and delayed type hypersensitivity (DTH) response. Results obtained in the present study revealed marked suppression of humoral and CMI responses in a dose dependent pattern. Hence, suppression of immune responses by phosphamidon even at subchronic doses is clearly an important aspect for its safety evaluation.     

The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men

A comprehensive evaluation of the cellular immune system (total T-cell, helper cell, suppressor cell, and natural killer cell numbers; in vitro interleukin-2 production, T-cell responses to mitogens and antigens, serum beta 2 microglobulin levels, and delayed hypersensitivity skin tests) was performed on 36 HTLV-III seronegative and 16 HTLV-III seropositive healthy homosexual men, 48 asymptomatic homosexual men with the chronic lymphadenopathy syndrome, 41 patients with AIDS, and 29 heterosexual controls without any known risk factors for AIDS. Our studies demonstrate that HTLV-III seronegative homosexual men have normal cellular immunity and are comparable to heterosexual controls. The abnormalities of lymphocyte subsets observed in HTLV-III seropositive healthy homosexual men are comparable to subjects with chronic lymphadenopathy. Assays of lymphocyte function, with the exception of delayed type hypersensitivity (DTH) skin tests, are similar in each group except patients with AIDS. Subjects with chronic lymphadenopathy were less responsive to DTH skin tests and HTLV-III seropositive healthy homosexuals were comparable to chronic lymphadenopathy subjects. We conclude that immunologic abnormalities in homosexual men are attributable to infection with HTLV-III.     

Neonatal immune challenge exacerbates experimental colitis in adult rats: potential role for TNF-alpha

Early life events and childhood infections have been associated with the development and onset of inflammatory bowel disease in adulthood. However, the consequences of neonatal infection in the development and severity of colitis are not established. We investigated the effects of a neonatal (postnatal day 14) or juvenile (postnatal day 28) immune challenge with LPS on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced damage and weight loss, as well as on food intake and body temperature in adult rats. Neonatally (n)LPS-treated rats developed more severe colitis than control animals, reflected in a greater loss of weight and a significantly increased macroscopic tissue damage score. These findings were associated with a hypothermic response after TNBS treatment in nLPS rats, but not in neonatally saline-treated rats receiving TNBS. These differences were not seen after TNBS in rats that had received LPS on postnatal day 28. Plasma corticosterone was measured as an index of adult hypothalamic-pituitary-adrenal (HPA) axis activation as was TNF-alpha, a proinflammatory cytokine associated with inflammatory bowel disease. Four days after TNBS treatment, plasma corticosterone was unaltered in all groups; however, TNF-alpha was significantly increased in adult TNBS-treated rats that had LPS as neonates compared with all other groups. In conclusion, neonatal, but not later, exposure to LPS produces long-term exacerbations in the development of colitis in adults. This change is independent of HPA axis activation 4 days after TNBS treatment but is associated with increased circulating TNF-alpha, suggestive of an exaggerated immune response in adults exposed to neonatal infection.     

Effect of neonatal exposure to 5-bromo-2'-deoxyuridine on life span, estrus function and tumor development in rats--an argument in favor of the mutation theory of aging?

Outbred LIO rats were exposed to subcutaneous injections (3.2 mg) of a synthetic analogue of thymidine, 5-bromo-2'-deoxyuridine (BrdUrd), on days 1 and 3, or days 1, 3, 7 and 21 of postnatal life. The mean life span decreased by 31% and 38% in male and by 14% and 27% in female rats that received 2 and 4 injections of BrdUrd, respectively, in comparison to untreated controls. The opening of the vagina was delayed, whereas age-related changes in the length of the estrous cycle and in the incidence of persistent estrus and/or anestrus were observed earlier in BrdUrd-injected female rats than in untreated ones. Inhibition of compensatory ovarian hypertrophy induced by hemiovariectomy at the age of 3 months was found in females exposed neonatally to BrdUrd as compared to untreated rats, while the uterus weight increase induced by the administration of human chorionic gonadotropin was similar in both control and BrdUrd-treated infantile rats. These data suggest that exposure to BrdUrd in early life impairs pituitary gonadotropic function in female rats. It was also shown that neonatal administration of BrdUrd to rats doubles the incidence of chromosome aberrations in peripheral blood lymphocytes in comparison to controls and is followed by a dose-related increase in tumor incidence. Our observations on the decrease in mean and maximum life span, acceleration of age-related changes in reproductive system function, increase in chromosome aberration and tumor incidence and decrease in tumor latency in rats exposed to BrdUrd in early life suggest that this model could be used as a model of accelerated aging and that some of the results can be interpreted as arguments in favor of the mutation theory of aging.     

Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma

The role of B cells in T-cell priming is unclear, and the effects of B-cell depletion on immune responses to cancer vaccines are unknown. Although results from some mouse models suggest that B cells may inhibit induction of T cell-dependent immunity by competing with antigen-presenting cells for antigens, skewing T helper response toward a T helper 2 profile and/or inducing T-cell tolerance, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory. We assessed immune responses to a well-characterized idiotype vaccine in individuals with severe B-cell depletion but normal T cells after CD20-specific antibody-based chemotherapy of mantle cell lymphoma in first remission. Humoral antigen- and tumor-specific responses were detectable but delayed, and they correlated with peripheral blood B-cell recovery. In contrast, vigorous CD4(+) and CD8(+) antitumor type I T-cell cytokine responses were induced in most individuals in the absence of circulating B cells. Analysis of relapsing tumors showed no mutations or change in expression of target antigen to explain escape from therapy. These results show that severe B-cell depletion does not impair T-cell priming in humans. Based on these results, it is justifiable to administer vaccines in the setting of B-cell depletion; however, vaccine boosts after B-cell recovery may be necessary for optimal humoral responses.     

Effect of prenatal androgen treatment on maternal behavior in the female rat

The perinatal critical period when androgen suppresses the capacity of virgin female rats to display maternal behavior in response to pups in adulthood was studied. A single direct injection of a large dose of testosterone propionate (TP) to the fetuses on Days 19 or 21 of pregnancy, but not during the neonatal period, significantly suppressed maternal responses in females. Percentages of females with anovulatory ovaries were largest in groups treated with TP within 2 days after birth. It is suggested that the androgen-sensitive period of the maternal mediating systems in the female rat exists prenatally, whereas the critical period of the systems regulating the cyclic release of ovulatory hormone is in the neonatal period.     

Immune responses following neonatal DNA vaccination are long-lived, abundant, and qualitatively similar to those induced by conventional immunization

Virus infections are devastating to neonates, and the induction of active antiviral immunity in this age group is an important goal. Here, we show that a single neonatal DNA vaccination induces cellular and humoral immune responses which are maintained for a significant part of the animal's life span. We employ a sensitive technique which permits the first demonstration and quantitation, directly ex vivo, of virus-specific CD8(+) T cells induced by DNA immunization. One year postvaccination, antigen-specific CD8(+) T cells were readily detectable and constituted 0.5 to 1% of all CD8(+) T cells. By several criteria-including cytokine production, perforin content, development of lytic ability, and protective capacity-DNA vaccine-induced CD8(+) memory T cells were indistinguishable from memory cells induced by immunization with a conventional (live-virus) vaccine. Analyses of long-term humoral immune responses revealed that, in contrast to the strong immunoglobulin G2a (IgG2a) skewing of the humoral response seen after conventional vaccination, IgG1 and IgG2a levels were similar in DNA-vaccinated neonatal and adult animals, indicating a balanced T helper response. Collectively, these results show that a single DNA vaccination within hours or days of birth can induce long-lasting CD8(+) T- and B-cell responses; there is no need for secondary immunization (boosting). Furthermore, the observed immune responses induced in neonates and in adults are indistinguishable by several criteria, including protection against virus challenge.     

Early stress and genetic influences on hypothalamic-pituitary-adrenal axis functioning in adulthood.

During early development, environmental challenges set the stage for permanent changes in the functioning of the pituitary-adrenal stress response. Since these data have been reported almost exclusively in single rat strains the role of phenotypic and genotypic factors in shaping the stress response is relatively unknown. This study examined whether the phenotypic/genetic profile of the rat influences the long-term response to challenge after early exposure to stress. Two strains of Sprague-Dawley rats were used in this study: one is a stress-induced animal model of "learned helpless" (LH) behavior and the other a resistant strain developed through selective breeding. Stress-induced adrenocorticotropic hormone (ACTH) and corticosterone release was monitored in adult congenital learned helpless (cLH) rats and congenital non-learned helpless (cNLH) rats. The rats were exposed to cold stress or maternal deprivation (on either postnatal day 7 or day 21). After the early acute stress exposure, animals remained undisturbed until challenged in adulthood (day 90) with footshock stress. In cLH animals (adults) early cold stress (particularly after acute stress on postnatal day 21) and maternal deprivation stress resulted in an enhancement of stress-induced ACTH release compared to nonstressed cLH and cNLH controls. In contrast, adrenal responsiveness was generally suppressed in cLH animals that were acutely stressed with cold stress or maternal deprivation stress early in life. The above results suggest that the genetic/phenotypic profile of the animal is a determinant in the changes observed in the adult stress response after early exposure to stressors.     

Dim Light at Night Increases Immune Function in Nile Grass Rats,a Diurnal Rodent

With the widespread adoption of electrical lighting during the 20th century, human and nonhuman animals became exposed to high levels of light at night for the first time in evolutionary history. This divergence from the natural environment may have significant implications for certain ecological niches because of the important influence light exerts on the circadian system. For example, circadian disruption and nighttime light exposure are linked to changes in immune function. The majority of studies investigating the effects of light exposure and circadian disruption on the immune system use nocturnal rodents. In diurnal species, many hormones and immune parameters vary with secretion patterns 180° out of phase to those of nocturnal rodents. Thus, the authors investigated the effects of nighttime light exposure on immunocompetence in diurnal Nile grass rats (Arvicanthis niloticus). Rats were housed in either standard 14-h light (L):10-h dark (D) cycles with L ～150 lux and D 0 lux or dim light at night (dLAN) cycles of LD 14:10 with L ～150 lux and D 5 lux for 3 wks, then tested for plasma bactericidal capacity, as well as humoral and cell-mediated immune responses. Rats exposed to dLAN showed increased delayed-type hypersensitivity pinna swelling, which is consistent with enhanced cell-mediated immune function. dLAN rats similarly showed increased antibody production following inoculation with keyhole lymphocyte hemocyanin (KLH) and increased bactericidal capacity. Daytime corticosterone concentrations were elevated in grass rats exposed to nighttime dim light, which may have influenced immunological measures. Overall, these results indicate nighttime light affects immune parameters in a diurnal rodent. (Author correspondence: fonken.1@osu.edu)     

Study of the immunotropic activity of aminoglycoside antibiotics

The action of some aminoglycoside antibiotics on the immune system was studied on both intact mice and the animals with immune deficiency caused by administration of cyclophosphamide. The following tests were used: local hemolysis (the Herne test), lymphocyte transformation (LT), delayed hypersensitivity to sheep red blood cells and the local graft versus host reaction (GVHR). Amikacin was shown to have no significant action on the activity of lymphocytes in the intact mice and stimulated both cellular (LT and GVHR) and humoral (the Herne test) immunity in the animals with lowered immunological reactivity. Sisomicin had no significant action on the immune system of the animals. Gentamicin suppressed the immune response only in the intact mice. Kanamycin and streptomycin induced inhibition of humoral and cellular immunity in both the intact mice and animals with immune deficiency. On the basis of the results it was concluded that gentamicin, amikacin and sisomicin may be used in the treatment of diseases developing in the presence of immune deficiency whereas streptomycin and kanamycin should be recommended when inhibition of the immunity is needed.     

低氧对新生大鼠脾单个核细胞DNA合成及转化的影响

本研究以荧光法测定脾单个核细胞ＤＮＡ合成及ＭＴＴ比色法测定的脾单个核细胞对ＣｏｎＡ的增殖反应,观察模拟高原低氧对出生后１４天大鼠上述两指标的影响,同时也观察了交感神经和副交感神经的活动状态,以初步探讨低氧对上述两指标的作用是如何介导的。结果表明：５ｋｍ海拔高度低氧作用２４ｈ不抑制脾单个细胞ＤＮＡ合成及脾单个核细胞转化,而作用５天时则抑制ＤＮＡ合成及脾单个核细胞转化,分别为对照组的５６．６％（Ｐ＜０．０１）和８６．８％（Ｐ＜０．０５）;７ｋｍ海拔高度低氧作用２４ｈ,ＤＮＡ合成及脾单个核细胞转化均受抑制,分别为对照组的６１．０％（Ｐ＜０．０１）和８１．２％（Ｐ＜０．０１）;７ｋｍ海拔２４ｈ低氧导致脾脏中乙酰胆碱下降,儿茶酚胺升高;用ＤＳＰ－４中枢药理性损毁ＮＥ神经元,可使脾单个核细胞ＤＮＡ合成的抑制程度减弱,脾脏中儿茶酚胺含量下降。这些结果表明低氧可抑制新生大鼠脾单个核细胞的ＤＮＡ合成及转化,并可能与交感神经兴奋及副交感神经抑制有关