THE IN-VIVO EFFECTS OF INTERLEUKIN-3 ON HISTAMINE LEVELS IN NON-HODGKINS-LYMPHOMA PATIENTS

Recombinant human Interleukin-3 (RhIL-3) is a haemopoietic growth fact or with effect both on early and differentiated cells, such as eosinop hils and basophils, and it also acts as a histamine-releasing agent. T he purpose of the present study was to examine whether in vivo rhIL-3 administration after chemotherapy affected basophil histamine levels a nd whether a concordance between rhIL-3 induced histamine release and side effects during the treatment could be demonstrated. Thirty patien ts with non-Hodgkin's lymphoma entered the study. All patients receive d 6 courses of chemotherapy, rhIL-3 was administered subcutaneously on ce daily after the second and the fourth course of chemotherapy from c ycle day 2-15 at the dose levels 0.5, 1.0, 5.0, 7.5 and 10 mu g/kg wit h 6 patients at each dose level. In cycle 6 recombinant human Granuloc yte-Macrophage Colony-Stimulating Factor (rhGM-CSF) (3.0 mu g/kg) was administered sequential/concurrent day 9-15 to rhIL-3 (day 2-15) at al l dose levels except 7.5 mu g/kg, where rhIL-3 was given day 2-8 and r hGM-CSF sequential day 9-15. Cycles 1, 3 and 5 served as control cycle s with no cytokine therapy. During rhIL-3 treatment, and after CHOP ch emotherapy, the basophil counts increased moderately especially during the recovery period day 15-22, and mainly at the two highest dose lev els 7.5 and 10 mu g/kg, but never exceded the normal upper limit. Hist amine levels in basophils were the same in patients before chemotherap y and healthy volunteers, and except from a trend to increased histami ne level at 10 mu g/kg on day 15, no difference was noted between rhIL -3 cycles and control cycles. Within 3-4 hr after rhIL-3 administratio n, a drop in histamine level in basophils was noted, which could be du e to histamine-releasing properties of rhIL-3 as previously demonstrat ed by in vitro studies. No serious side effects were noted during the cytokine treatment, and despite that most patients had mild flushing o f the face, neck and upper chest, no patients experienced sensitizatio n throughout the study. Although a significant increase in rhIL-3-indu ced histamine release from basophils was noted in some of the patients , no correlation to the dose of rhL-3 was found, and no correlation wa s noted between side effects and histamine release or histamine levels in basophils.