In vivo suppression of plasma IL-12 levels by acute and chronic stress paradigms: potential mediating mechanisms and sex differences.
Interleukin-12 (IL-12) is a major pro-inflammatory cytokine, which promotes cell-mediated immunity and T(H)1 differentiation. In vitro studies indicated suppression of IL-12 production by several stress-related factors, but no effects of behavioral stress were shown on plasma IL-12 levels. Therefore, in the current study we (i) examined the in vivo effects of various behavioral and pharmacological stress paradigms on baseline plasma IL-12 levels; (ii) compared these in vivo findings to those obtained following in vitro stimulation of leukocytes from the same rats; and (iii) assessed potential sexual dimorphism in these outcomes. The findings indicated that plasma IL-12 levels were significantly reduced by social confrontation, wet-cage exposure, surgery, and the administration of corticosterone, epinephrine, or prostaglandin-E(2). Notably, most in vivo impacts on plasma levels were not evident when assessed in vitro. The IL-12-reducing effects of wet-cage exposure, and of corticosterone and epinephrine administration, were significantly greater in males than in females, although females exhibited greater total corticosterone levels following stress. The duration of acute stressors predicted the degree of IL-12 reduction, but more prolonged stressors did not. Furthermore, seven days of alternating behavioral stressors reduced plasma IL-12 levels more than 14 days. These findings suggest animals' behavioral habituation to stress conditions, or a specific immune mechanism restricting the duration of IL-12 reduction. Overall, our findings indicate a generic and robust stress-induced reduction in plasma IL-12 levels, and suggest epinephrine, corticosterone, and prostaglandin-E(2), as potential mediators that should be scrutinized in vivo in the context of natural physiological stress responses.
Neuroimmunology Research Unit, Department of Psychology, Tel-Aviv University, Tel-Aviv, Israel.
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Shaashua
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Sominsky
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Levi
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Sorski
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Reznick
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Ben-Eliyahu
D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004777:Environment; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006799:Housing, Animal; D018664:Interleukin-12 / Q000097:blood*; D007813:Laparotomy; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D012149:Restraint, Physical; D012727:Sex Characteristics; D012931:Social Environment; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood*; D013550:Swimming / Q000523:psychology
C527702:CpG ODN 2395; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D015232:Dinoprostone; D003345:Corticosterone; D004837:Epinephrine