Influence of pain stimulation on interleukin-2 production in mice.

We previously demonstrated that plaque-forming cell (PFC) production in the spleen of mice immunized with sheep red blood cells (SRBC) was enhanced by pain stimulation. This phenomenon was due to activation of antigen nonspecific L3T4-/Lyt-2- T lymphocytes (double-negative T cells) by the beta-adrenergic action of endogenous catecholamines released from the adrenal gland after pain stimulation. Further study also demonstrated that interleukin-2 (IL-2) production of spleen cells was enhanced in mice by pain stimulation. In this study spleen cells of BALB/c mice were cultured with Con A and SRBC, respectively, and the IL-2 level was measured by incorporation of 3H-thymidine into CTLL-2 cells during culture for 24 hours. Interleukin-2 production of spleen cells from mice given pain stimulation was significantly increased compared with spleen cells of normal mice. The IL-2 production of spleen cells of normal mice was also markedly enhanced by the mixed culture with spleen cells from pain-stimulated mice. Enhancement of IL-2 production in the spleen cells of mice given pain stimulation did not occur with anti-Thy-1.2 antibody and complement treatment, but production was maintained by treatment with anti-L3T4 antibody and complement. These data suggest that the enhanced production of IL-2 in mice given pain stimulation resulted from the activation of L3T4- T cells by endogenous catecholamines released from the adrenal gland after pain stimulation. It can be assumed that activated L3T4- T cells interact with antigen-specific L3T4+ T cells and lead to enhanced IL-2 production.