In vivo production of type 1 cytokines in healthy sickle cell disease patients.

Interleukins (IL)-1, 2, 12, and interferon (IFN)-gamma, along with soluble IL-2 receptor (sIL-2R) were measured from sera obtained from healthy sickle cell disease (SCD) patients and comparable healthy control subjects. The cytokines were assessed by enzyme-linked immunosorbent assay (ELISA) in 60 SCD patients and 58 controls. No significant detectable levels of IL-1 or IL-12 were found in the sera of either group of patients. Significantly elevated levels of IFN-gamma were measured in 20 (33%) of 60 SCD patients and 21 (36%) of 58 controls. A large subset of 18 (41%) of 43 healthy controls and a smaller subset of 12 (21%) of 58 SCD demonstrated detectable levels of IL-2. The sIL-2R levels of the SCD group (4465 +/- 552 pg/mL) were significantly higher (P < .0001) than that of controls (3473 +/- 411 pg/mL). The results revealed comparable circulating levels of all type 1 cytokines in both healthy SCD and normal control subjects, with the exception of in vivo sIL-2R production. Elevated serum levels of both IL-6 and tumor necrosis factor (TNF)-alpha have been reported previously in a significant percentage of SCD steady-state subjects. These two cytokines are known to increase sIL-2R expression and may help explain the difference between the patient populations. Immune activation markers such as sIL-2R are produced by cells that mediate host responses to infection or inflammatory stimuli. The implication of higher levels of sIL-2R in SCD is not clear, but chronic parvovirus B19 infection, chronic polyclonal activation of B cells or defective regulation of antibodies are possible explanations for the elevated levels in SCD.