Antihistaminic drugs modify casein-induced inflammation in the rat.
BACKGROUND
All known antihistaminics may affect several inflammatory events, including chemotaxis, the survival of eosinophils, and the release of chemokines and cytokines from different sources, thus highlighting the potential for modulating chronic inflammation and immune responses. The aim of the study was to examine the effect of H(1)-H(4) antihistaminic drugs in an acute model of casein-induced inflammation in rat.


METHODS
Inflammation was induced by injection of a 12% solution of casein into the peritoneal cavity of male Wistar rats. The rats were treated intraperitoneally with pyrilamine maleate (10 mg/kg), cimetidine (25 mg/kg), thioperamide maleate (2 mg/kg) or ciproxifan hydrogen maleate (0.14 mg/kg) twice: 2 hours prior and 4 hours after casein administration. The level of histamine in blood and chemiluminescence of stimulated and unstimulated PMNs was measured.


RESULTS
The level of histamine in the casein-induced inflammation group was higher than in the control group. Treatment with pyrilamine and ciproxifan additionally increased the level of blood histamine during the inflammatory response. Peripheral blood neutrophils from rats with casein-induced inflammation tended to respond less to zymosan stimulation than the neutrophils in the controls. Selective H(1) and H(3) antagonists injected into the rats with casein-induced inflammation significantly increased the response of the neutrophils to zymosan (p < 0.01).


CONCLUSIONS
Histamine produced or released into the blood in the course of experimental inflammation exerts its effects on the PMN-s via stimulation of H(1) and H(3) receptors.
Rzodkiewicz
P
P
Department of Biochemistry, Institute of Rheumatology, Warsaw, Poland. przemyslaw.rzodkiewicz@ir.ids.pl
Wojtecka-Lukasik
E
E
Szukiewicz
D
D
Schunack
W
W
Maslinski
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents; D002364:Caseins; D006632:Histamine / Q000097:blood; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D049449:Luminescence; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
D000893:Anti-Inflammatory Agents; D002364:Caseins; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D054828:Histamine H3 Antagonists; C498828:Hrh4 protein, rat; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine