Defective IL-6 secretion in HIV-infected haemophilia patients.

Abstract

To study the role of IL-6 in HIV-induced B cell defects, in vitro B cell responses and IL-6 secretion were determined simultaneously in 67 haemophilia patients. Twenty-three patients were HIV- (Group 1), 27 HIV+ stage CDC II, III (Group 2), and 17 were HIV+ stage CDC IV (Group 3). Pokeweed mitogen (PWM) was used for T cell-dependent and Staphylococcus aureus Cowan I (SAC I) for T cell-independent B cell stimulation. B cell differentiation was assessed in a reverse haemolytic plaque assay and by ELISA determination of IgG and IgM in culture supernatants. An ELISA was used to measure IL-6 in plasma and culture supernatants. HIV- patients showed impaired immunoglobulin-secreting cell (ISC) responses after T cell-independent and T cell-dependent stimulation (P < 0.0001 and P < 0.01, respectively), whereas IL-6 secretion, IgM and IgG responses were comparable to those in healthy controls. HIV+ patients at stage CDC II, III or IV demonstrated significantly reduced mitogen-stimulated IL-6 secretion (P < 0.05, PWM; P < or = 0.001, SAC I) as well as impaired ISC and IgG responses (P < 0.01, PWM; P < or = 0.0001, SAC I). CDC IV patients showed reduced IgM responses in addition (P < 0.02, PWM; P < 0.0005, SAC I). Plasma IL-6 levels were elevated both in HIV+ patients (CDC II, III patients: 165 +/- 73 pg/ml, P < 0.005; CDC IV patients: 58 +/- 18 pg/ml, P < 0.0001) and in HIV- patients (283 +/- 65 pg/ml, P < 0.0001) which appeared to be a T cell effect induced by treatment with haemophilia factor concentrates. Our data provide evidence for different types of B cell deficiencies in HIV- patients (impaired ISC response only) and HIV+ patients (impaired ISC as well as IL-6 and IgM/IgG responses). The defective IL-6 secretion in HIV+ patients is likely to affect terminal B cell differentiation and this may explain the reduced immunoglobulin secretion in these patients in response to antigenic challenge.