Role of histamine in the antitumour activity of endotoxin.
The role of histamine in the antitumour activity of endotoxin against solid syngeneic Meth-A sarcoma in BALB/c mice was studied. Endotoxin induces haemorrhagic necrosis and regression of this tumour. Histamine and the selective H1 receptor agonist 2-pyridylethylamine mimicked the induction of necrosis but did not cause regression. The selective H2 receptor agonist dimaprit did not cause any tumour damage. The effect of histamine could be inhibited by the H1 receptor antagonists diphenhydramine and promethazine but not by the H2 receptor antagonist cimetidine. Endotoxin-induced necrosis was slightly affected by diphenhydramine, and the incidence of regression was reduced by both H1 antagonists. Cimetidine potentiated endotoxin-induced regression. Similar effects were observed concerning the effects of H-receptor antagonists on necrosis and regression induced by tumour necrosis serum (TNS). Histological examination revealed no marked additional effects of diphenhydramine or cimetidine on endotoxin-induced hyperaemia, haemorrhagic necrosis, and mitotic arrest of the tumour cells. Only cimetidine increased the extent of nonhaemorrhagic necrosis. The endotoxin-induced release of tumour necrosis factor and cytostatic activity in TNS was clearly reduced by diphenhydramine, but hardly affected by cimetidine. Data indicate that intact H1 receptors are required for the induction of tumour regression and antitumour factors by endotoxin. Concomitant H2 blockade may facilitate this by stimulating H1 receptor-mediated processes upon endotoxin-induced histamine release, although a cimetidine-induced inhibition of T-suppressor cell activation might also be involved.
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology; D006632:Histamine / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000209:etiology; D011398:Promethazine / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha
D004731:Endotoxins; D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D011398:Promethazine