Interleukin 6 and C-reactive protein levels in patients with acute allergic reactions: an emergency department-based study

Background: Elevations of interleukin 6 (IL-6) have been described in drug- induced anaphylaxis. Although IL-6 is well known to stimulate an acute phas e response, profiling acute phase protein levels, such as C-reactive protei n (CRP), has, to our knowledge, never been performed in patients with acute allergic reactions. Objective: To examine the pattern of IL-6 and CRP levels in patients with a cute allergic reactions and to relate these to relevant clinical and labora tory parameters. Methods: Plasma CRP and serum IL-6 levels were determined in 85 adult emerg ency department patients. These patients had been previously studied with q uestionnaires, physical examinations, and histamine/tryptase levels. Clinic al and historical features were related to CRP and IL-6 levels. CRP and IL- 6 levels were also examined for relationships with histamine and tryptase l evels. Results: CRP and IL-6 levels were significantly correlated with one another in the study patients (Spearman rho = 0.36, P = 0.0008). Similar to histam ine levels, IL-6 levels were significantly correlated with the extent of er ythema manifested by the study patients. The extent of erythema was indepen dently predicted by both IL-6 and histamine levels. Histamine levels were n egatively correlated with CRP levels (Spearman rho = -0.32, P = 0.003). Unl ike histamine levels, IL-6 and CRP did not show significant relationships w ith the extent or presence of urticaria/angioedema or the presence of wheez ing. IL-6 levels were correlated with the duration of symptoms before serol ogic sampling. An inverse correlation was observed between IL-6 levels and mean arterial blood pressure. Multivariate modeling showed significant inde pendent effects from mean arterial pressure, duration of symptoms, erythema extent, and age in predicting IL-6 levels. Tryptase levels were higher in patients whose IL-6 levels were > 20 pg/mL. Conclusions: CRP and IL-6 levels are not simple surrogate markers for hista mine or tryptase release by mast cells or basophils in acute allergic react ions. Increasing IL-6 levels relate to greater erythema extent, lower mean arterial blood pressure, and a longer duration of symptoms. It would be int eresting to speculate that CRP and IL-6 increases characterize a late-phase response in immediate hypersensitivity reactions. In this perspective, the inverse relationship between CRP and histamine levels could be explained. As histamine levels are waning, CRP levels are increasing. Timed studies fo r histamine and CRP/IL-6 levels in allergic reactions are necessary to conf irm this hypothesis.