Interleukin-6 is released in the cutaneous response to allergen challenge in atopic individuals.

The mechanisms responsible for cutaneous response to antigen are complex. Interleukin-1 (IL-1) and interleukin-6 (IL-6) are proinflammatory cytokines that share many properties. Previous studies with a blister-chamber model have demonstrated IL-1 to be produced in the cutaneous response to antigen. Since IL-2 production by activated T cells and IL-6 production by macrophages are both stimulated by IL-1, we hypothesized that IL-2 and IL-6 may be involved in the cutaneous late-phase response (LPR) to antigen. We examined antigen-challenged sites for IL-2 immunoreactivity (ELISA) but found no difference between antigen- and diluent-challenged skin sites (N = 4). Since IL-2 has been demonstrated to be produced in response to IL-1 and IL-1 activity has been demonstrated to be greatest between hours 10 and 12, we speculated that IL-2 might not be detected until after hour 12. We were unable to demonstrate any increase in IL-2 production, even by extending our studies to 24 hours in two subjects. Antigen-challenged, skin blister-chamber fluids from atopic subjects demonstrated the appearance of IL-6 (ELISA) in pooled samples representing hours 1 1/2, 3 1/2, 5 1/2, and 7, but not at diluent control sites (p less than 0.05; N = 6). IL-6 reached a median peak of 0.66 ng/ml at 3 1/2 hours. Median levels of IL-6 fell to baseline at 8 hours, followed by a second peak of 0.25 ng/ml at hour 10. Three distinct patterns of IL-6 release were noted: early release of IL-6 followed by a sustained slower rise that peaked at hour 9 before declining to baseline levels at 12 hours, early release of IL-6 followed by a fall to baseline levels at hours 7 to 9 with a second smaller peak at hours 9 to 11, and isolated early release of IL-6. Early IL-6 production correlated with late histamine production (R = 0.801; p = 0.06), and late IL-6 production correlated with eosinophil influx (R = 0.813; p = 0.05). The area of the LPR at skin test sites correlated with early IL-6 peak levels (R = 0.977; p = 0.004) and with total early IL-6 production (R = 0.885; p = 0.05), but not with late IL-6 production.(ABSTRACT TRUNCATED AT 400 WORDS)

Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade.

Anaphylaxis to known allergens occurred in two patients under treatment for hypertension with propranolol. The clinical course of both cases was similar. Bradycardia associated with an undetectable blood pressure, unusual severity, and sluggish response to treatment were major common factors in which blockade of the beta-adrenergic system may have had a role. Propranolol, a beta-adrenergic antagonist that acts competitively by blocking the adenylate cyclase receptor on efferent cells, is well recognized to cause increased airways resistance in some asthmatic and normal subjects. It is postulated that propranolol potentiated anaphylaxis in these patients by inhibition of adenylate cyclase, resulting in lowered intracellular cyclic AMP and a lowered threshold of mediator release. The bradycardia during profound hypotension is attributed to an unopposed cholinergic action caused by blunting of the normal endogenous beta-adrenergic response by propranolol.