Defective IL-6 secretion in HIV-infected haemophilia patients

Abstract

SUMMARY 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 palients were HIV (Group 1). 27 HIV+ stage CDC II, III (Group 2). and 17 vi-ere HIV4 stage CDC IV (Group 3). Pokeweed mitogen (PWM) was used for TeelI-dependent and Staphylococcus aureus Cowan 1 (SAC I) for T cell-independent B cell stimulalion. 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 < 0·000l and P<0·01, respectively), whereas IL-6 secretion. IgM and IgG responses were comparable to those in hcallhy controls. HIV+ patients at stage CDC II, Ml or IV demonst rated significantly reduced mitogen-stimulated IL-6 secretion (P < 0·05. PWM; P < 0·001. SAC lj as well as impaired ISC and IgG responses (P < 0·01. PWM; P≤ 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 < 0·001) 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 /lgG 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.