Attenuation of catecholamine-induced immunosuppression in whole blood frompatients with sepsis

Studies performed on healthy volunteers have revealed that catecholamines d own-regulate the lipopolysaccharide (LPS)-induced production of tumor necro sis factor (TNF)alpha, interleukin (IL)-6, and IL-1 beta. We extended this observation and show that this effect is based on changes in the mRNA conce ntration of these cytokines, Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when t he disease has proceeded to the state of prolonged hypotension. We here inv estigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and o f those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentra tion was determined. In blood of healthy volunteers, epinephrine reduced th e LPS-stimulated synthesis of TNF alpha by 62.5% (P < 0.0001), of IL-6 by 3 9% (P < 0.0001), and of IL-1 beta by 40% (P = 0.015), and increased the LPS -stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blo od of patients with prolonged severe sepsis, TNF alpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-lp and IL-10 w ere not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine l evels of IL-6 and IL-10, and decreased TNF alpha only by 36.4% (P < 0.0001) . Interestingly, epinephrine suppressed the IL-1 beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice a s much as in blood samples of healthy volunteers. The altered response of s eptic blood to catecholamines might be due to an altered reactivity of leuk ocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.