Induction of histidine decarboxylase, the histamine-forming enzyme, in mice by interleukin-12.
Interleukin (IL)-12, a potent antitumour cytokine, has inflammatory side effects. We examined the effect of IL-12 on the histamine-forming enzyme, histidine decarboxylase (HDC). When injected intraperitoneally into C3H/HeN mice, IL-12 exhibited antitumour activity against squamous epithelial tumour cells (NR-S1 cells). At doses that produced this antitumour activity, IL-12 also enhanced HDC activity in the lung, liver, spleen and bone marrow. Compared with that induced by IL-1, the elevation of HDC activity induced by IL-12 was low and slow. However, daily injections of IL-12, but not of IL-1, produced a cumulative effect on HDC activities, an accumulation of exudate in the thorax, and death. Antagonists of H1 and H2 receptors and an inhibitor of HDC all failed to prevent the pulmonary exudation and death. These results suggest that IL-12 is an inflammatory cytokine capable of stimulating the synthesis of histamine, but that histamine itself may be not the direct cause of the pulmonary exudation and/or lethality induced by IL-12.
Yamaguchi
K
K
Department of Oral and Maxillofacial Surgery (I), School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Motegi
K
K
Endo
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000096:biosynthesis; D006633:Histamine Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000096:biosynthesis*; D007249:Inflammation / Q000209:etiology; D007375:Interleukin-1 / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D007375:Interleukin-1; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018664:Interleukin-12; D006632:Histamine; D006640:Histidine Decarboxylase