SYSTEMIC INTERLEUKIN-1-ALPHA AND INTERLEUKIN-2 SECRETION IN RESPONSE TO ACUTE STRESS AND TO CORTICOTROPIN-RELEASING HORMONE IN HUMANS

Acute stress results in activation of the hypothalamic-pituitary-adreaal (HPA) axis. ACTH and cortisol secretion is stimulated by corticotropin-releasing hormone (CRH). It has also been shown that activation of the HPA axis during stress is accompanied by changes in the immune response. However, little is known about the influence of acute stress on the release of cytokines such as inteleukin-1 (IL-1) or interleukin-2 (IL-2). In this study, we determined serum IL-1 alpha and IL-2 levels in 19 patients undergoing the acute stress of angioplasty for coronary artery disease. A second protocol was devised to determine serum IL-1 alpha anti IL-2 concentrations as well as lymphocyte subpopulations in 10 normal volunteers receiving 1 mu g kg(-1) human CRH intravenously. Finally, IL-1 alpha concentrations were measured in CRH-incubated mononuclear cell (MNC) and monocyte cultures. In response to the stress of angioplasty, ACTH and cortisol as well as IL-1 alpha and IL-2 concentrations were clearly above baseline levels (IL-1 alpha, mean +/- SEM, baseline: 1.39 +/- 0.34 ng ml(-1) after angioplasty: 2.64 +/- 0.73 ng ml(-1), P < 0.05 IL-2, baseline: 1.2 +/- 0.13 ng ml(-1), after angioplasty: 2.8 +/- 1.14 ng ml, P < 0.05). A similar pattern was obtained in normal subjects in response to CRH (Il-1 alpha, baseline: 0.8 +/- 0.2 ng ml(-1), after angioplasty: 3.7 +/- 1.4 ng ml(-1), P < 0.05 IL-2, baseline: 1.9 +/- 0.4 ng ml(-1) after angioplasty: 5.4 +/- 2.2 ng ml(-1), P < 0.02). The percentage of IL-2 receptor-positive lymphocytes rose from 3.9 +/- 1.2% to 6.2. +/- 1.6% (P < 0.05), the relative number of CD-3 lymphocytes rose from 74.5 +/- 1.6% to 78.3 +/- 2.0% (P < 0.05). No significant changes were observed in the number of CD-4, CD-8, natural killer and B cells. In vitro, IL-1 alpha concentrations in cultures containing CRH were not significantly different from control cultures. Our data demonstrate significant activation of the HPA axis and secretion of IL-1 alpha and IL-2 in response to both angioplasty and CRH. Furthermore, CRH administration resulted in activation of the cellular immune system (indicated by an increase in IL-2 receptor positive lymphocytes). Our in vitro data suggest that CRH may not directly act on blood mononuclear cells to induce IL-1 alpha release or, alternatively, sources other than blood mononuclear cells may account for the elevated IL-1 alpha levels observed in vivo. We conclude that CRH may play a major role in neuroendocrine-immune interactions during acute stress.