IN-VITRO LYMPHOCYTE BLASTOGENIC RESPONSES AND CYTOKINE PRODUCTION IN SICKLE-CELL DISEASE PATIENTS WITH ACUTE PNEUMONIA

Background. Pulmonary infections continue to be a major cause of morbi dity and mortality in patients with sickle cell disease (SCD). Methods . In this study cell-mediated immunity in vitro was evaluated in 62 SC D patients (62 steady state and 16 with acute pneumonia) and compared with 44 normal controls (30 healthy and 14 with acute pneumonia). Lymp hocyte blastogenic responses to phytohemagglutinin, tetanus toroid and Candida albicans antigen were assessed in all subjects. In addition p roduction of tumor necrosis factor, alpha- and gamma-interferon (IFN) were assayed. Results. The results revealed comparable blastogenic res ponses to all three stimuli in all subjects except SCD patients with p neumonia. This group showed poor responses to all stimuli. The mean co unts per minute were decreased 65 to 90% when compared with the other patients. Cytokine production of IFN-alpha and TMF was equivalent in a ll subjects. Conversely IFN-gamma production in both SCD groups, stead y state (35 +/- 6 U/ml) and SCD with pneumonia (14 +/- 6 U/ml), was si gnificantly decreased when compared with those in normal healthy contr ols (65 +/- 14 U/ml) and with pneumonia (48 +/- 17 U/ml). On analysis of individual titers 15 of 62 (24%) steady state and 10 of 16 (63%) SC D patients with pneumonia were deficient in IFN-gamma production in vi tro. Conclusions. Acute pulmonary infections seem to have a profound e ffect on cell-mediated immunity in SCD. IFN-gamma deficiency, along wi th quantitative and qualitative T cell abnormalities, may represent si gnificant factors to explain the frequent and severe infections seen i n SCD.