Bacteria-derived human leukocyte interferons alter in vitro humoral and cellular immune responses

Cultures of gradient-purified human peripheral blood mononuclear cells (PBMC) have been employed to examine the effects of three bacteria-derived human leukocyte interferon subtypes on certain aspects of in vitro immune responses. The addition of highly purified IFN-alpha 1, -alpha 2, -alpha 2/alpha 1 to PMBC cultures stimulated with phytohemagglutinin (PHA) or pokeweed mitogen resulted in a significant suppression of the mitogenic response. This suppression required the presence of interferon in the cultures because pretreatment of cells and removal of interferon had no effect on their response to PHA. The presence of these interferons at 200 U/ml also caused a substantial reduction of human mixed-lymphocyte reactions (MLR) as measured by [3H]thymidine incorporation by responder cells. Interestingly, pretreatment of stimulator cells was sufficient for this reduction to occur whereas pretreatment of responder cells had no effect on their ability to respond to allogenic stimulation. In contrast to these suppressive effects, the three interferons enhanced human in vitro primary immune response to sheep red blood cells (SRBC). These data demonstrate that both purified interferon subtypes and genetic hybrids of human interferons produced by recombinant DNA technology have effects on in vitro immune responses.     

Hyperinsulinemia in obesity: significance of adipose tissue cell size

Adipose tissue biopsy and an oral glucose tolerance test (OGTT) (50 g) were performed in 17 non-hyperlipoproteinemic subjects without overt diabetes mellitus. All the persons were weight stable at the time of investigation. A significant correlation between fasting insulin concentration and the mean adipocyte size was observed, whereas no correlation was noted between the ideal body weight index and fasting insulin level. Persons with larger adipocytes had elevated insulin levels as well as higher and longer lasting increments following the glucose challenge. They also exhibited significantly higher mean glucose levels during the OGTT. When these patients were matched for glucose tolerance with the subgroup having smaller mean adipocyte sizes, the difference in insulin levels was still demonstrable. The importance of adipose cell enlargement regulating basal and stimulated insulin output is underlined.     

Immune responses to environmental antigens that act on the skin: the role of lymphokines in contact dermatitis.

Immune responses to enviornmental agents affecting the skin may take various clinical forms, among which contact dermatitis is the most prominent representative of delayed-type hypersensitivity. Whereas in industrialized countries a relatively restricted amount of chemical agents is responsible for the majority of contact dermatitis cases, other factors from the environment such as natural flora, seasonal or nutritional factors may also play a role. Like other immune responses, contact dermatitis is strongly influenced by genetic factors and the existence of immune response genes, in part linked to the major histocompatibility complex, has been established in experimental animals. Whereas the formation of conjugates between skin-specific proteins and contactant allergens is held by some to represent an important feature in contact dermatitis, recent experiments suggest that the direct binding of contactants to monocyte and lymphocyte membranes represents the most efficient way in inducing sensitization of the T lymphocytes primarily responsible for contact hypersensitivity. At the effector level, complete inhibition of contact dermatitis and other delayed type hypersensitivity reactions by an antiserum prepared against guinea pig lymphokines (especially migration inhibition factor) offers strong evidence that lymphokines, as products of activated lymphocytes, also play a decisive role in vivo. The properties of antibodies raised against purified lymphokine fractions are reviewed. Localized contact dermatitis reactions, as well as accompanying phenomenons such as flar-up reactions and generalized maculopapular rashes, may, however, still involve other elements than T lymphocytes and lymphokines. The participation of other secondary cell types and of local antibody formation is briefly discussed.     

IL-3 and IL-5 prime normal human eosinophils to produce leukotriene C4 in response to soluble agonists

Eosinophils (Eos) produce large amounts of leukotriene C4 (LTC4) and platelet-activating factor (PAF) in response to calcium ionophore. However, the capacity of naturally occurring soluble agonists to promote lipid mediator formation by Eos is largely unknown. Our previous studies on neutrophils and basophils showed that certain hematopoietic growth factors are important regulators of lipid mediator formation. We examined LTC4 production by normal human Eos from healthy donors in response to soluble agonists with or without preincubation with the cytokines IL-3 and IL-5. Among three agonists (FMLP, C5a, PAF) tested over a wide concentration range, only FMLP induced some LTC4 formation by itself in normal Eos. However, after preincubation with IL-3 or IL-5, Eos produced detectable amounts of LTC4 in response to all three agonists. Eos primed by IL-3 or IL-5 generated at least 1 order of magnitude more LTC4 in response to FMLP as compared to C5a or PAF. FMLP-induced LTC4 production was enhanced by 26 to 635% (n = 16) and 67 to 611% (n = 12) after preincubation with IL-3 or IL-5, respectively. Priming for LTC4 production was concentration dependent occurring at IL-3 or IL-5 concentrations of 3 to 30 ng/ml and required an optimal preincubation period of 90 min. Thus, IL-3 and IL-5 profoundly modulate the production of lipid mediators by Eos in response to the soluble agonists FMLP, C5a, and PAF. Our data further support the importance of these cytokines in inflammatory reactions involving Eos.