Murine tumor necrosis factor-alpha sensitizes plasma corticosterone activity and the manifestation of shock: modulation by histamine.

Murine tumor necrosis factor-alpha (mTNF-alpha) results in the sensitization of mechanisms underlying plasma corticosterone activity and sickness behavior, the latter being reminiscent of septic or anaphylactic shock. The mTNF-alpha induced a sensitization of sickness and corticosterone in mice that was attenuated by pretreatment with the combinations of histamine H(1) (diphenhydramine, mepyramine) and H(2) (cimetidine) antagonists. Likewise, coadministration of diphenhydramine and cimetidine prevented the mTNF-alpha-provoked rise of monoamine activity within the posterior hypothalamus. Although dexamethasone ameliorated the mTNF-alpha-induced sensitization of corticosterone, illness behavior was unaffected. It is suggested that mTNF-alpha-induced illness and the neuroendocrine sensitization are mediated by endogenous histamine.