Attenuated monocyte IL-10 production in glucose-6-phosphate dehydrogenase-deficient trauma patients.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the world's most common known human genetic polymorphisms, but the pathophysiology of the defect remains largely unknown. In the present study, we compared hematology parameters and ex vivo monocyte cytokine responses in non-deficient and G6PD-deficient trauma patients. Deficient and non-deficient, moderately injured, trauma patients exhibited similar hematology profiles at the time of hospital admission. In contrast to non-deficient patients, G6PD-deficient patients were anemic 2 days post-injury. Monocytes from deficient individuals produced 50% less interleukin 10 (IL-10) in response to LPS and >90% less IL-10 in response to PMA, compared with non-deficient patients, 2 days post-injury. The presence of phenylhydrazine-treated, opsonized, autologous RBC (OX-RBC), alone had no effect on IL-10 production by non-deficient or deficient monocytes, whereas IL-10 responses to lipopolysaccharide (LPS) were augmented by OX-RBC in both groups. However, IL-10 production was markedly lower by monocytes from G6PD-deficient than non-deficient patients after stimulation with LPS plus OX-RBC. TNF-alpha production following PMA was similar in deficient and non-deficient patients, and the differences following LPS or LPS plus OX-RBC stimulation were moderate between deficient and non-deficient samples. Interferon (IFN)-gamma production ex vivo was doubled by OX-RBC treatment alone, but it was not stimulated by LPS treatment. IFN-gamma production was similar in non-deficient and G6PD-deficient patients. These data suggest that the observed differences in IL-10 responses between G6PD-deficient and non-deficient patients are not attributable to differences in TNF-alpha or IFN-gamma production. Taken together, our data suggest that a reduction in the capacity to produce IL-10 may be an intrinsic characteristic of G6PD-deficient monocytes. An attenuated IL-10 production may be a contributing mechanism in the previously observed augmented inflammatory response in severely injured G6PD-deficient compared with non-deficient trauma patients.