Influence of interleukin-1 beta on bradykinin-induced responses in guinea pig peritoneal macrophages.
OBJECTIVE
The endogenous nonapeptide bradykinin is implicated in the pathogenesis of a number of inflammatory diseases. Recently, it could be shown that bradykinin is a potent stimulus for the generation of arachidonic acid, prostaglandin E2 (PGE2) and superoxide radical via the bradykinin B2 receptor from macrophages depending on their stage of maturation or activation. The present study was designed to characterize the effect of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) on responsiveness of macrophages to bradykinin.


METHODS
Guinea pig peritoneal macrophages were collected 7 days after i.p. injection of paraffinum subliquidum.


RESULTS
The bradykinin-induced increase in cytosolic free calcium concentration ([Ca2+]i) and activation of the respiratory burst were significantly enhanced by interleukin-1 beta (100 U/ml) added to cultures of macrophages 24 h before stimulation with bradykinin. However, the EC50 values of bradykinin-induced calcium signal of 23 +/- 8 nM and 29 +/- 17 nM and superoxide radical formation of 64 +/- 22 nM and 34 +/- 29 nM in control and interleukin-1 beta-treated cells, respectively, were not changed. In contrast to the influence of IL-1 beta on these functions, saturation and competition experiments measured by binding of [3H]bradykinin ([3H]BK) to intact macrophages demonstrate that cell exposure to interleukin-1 beta for 24 h caused no change in the density and affinity of the bradykinin B2 receptors.


CONCLUSIONS
The most likely explanation for the cytokine effects is an influence on the level of the receptor-effector coupling downstream of the agonist binding.
Böckmann
S
S
Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Rostock, Germany.
Mohrdieck
K
K
Paegelow
I
I
D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism