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Pathological induced changes in beta-adrenoceptor function occur in diseases such as asthma and hypertension. The mechanism(s) of this dysfunction is at present unclear. In the present study, the effect of lymphokines on beta-adrenoceptor agonist induced cAMP production in peripheral blood mononuclear cells (PBMC) is investigated. Pre-incubation of PBMC during 20 h with interleukin-2 (IL-2, 100 u ml-1) and granulocyte/macrophage-colony stimulating factor (GM-CSF, 100 u ml-1) significantly decreases beta-adrenoceptor agonist induced cAMP production by 35 +/- 8% and 37 +/- 11% respectively. IL-3 and IL-4 do not affect beta-adrenoceptor agonist induced cAMP production in PBMC. It can be concluded that IL-2 and GM-CSF, mediators derived from T-lymphocytes, can induce beta-adrenoceptor dysfunction in PBMC.

The possible role of neutrophils and the endothelium in the induction of hyperreactivity of the pig coronary artery to histamine was studied. In pig isolated coronary arteries histamine caused a concentration-dependent contraction; maximal contraction to histamine, however, was reduced in endothelium-denuded arteries. Pre-incubation of intact coronary arteries with isolated neutrophils did not affect the contractile response to histamine, while pre-incubation of endothelium-denuded arteries induced a hyperreactivity to histamine. This induction of hyperreactivity to histamine by neutrophils in pig coronary arteries seems to be mediated by lipoxygenase products, since it could be prevented by pre-incubation of the preparations with lipoxygenase inhibitors, but not with inhibitors of cyclo-oxygenase or with scavengers.