Effects of interferon-alpha therapy on immune parameters in immune thrombocytopenic purpura.
Interferon-alpha (IFN alpha) has been shown to increase platelet numbers in patients with immune thrombocytopenic purpura (ITP), but the basis for this effect is not known. In this study changes in immune function were monitored following administration of IFN alpha to seven patients whose ITP had proved refractory to conventional therapy. Patients' peripheral blood mononuclear cells were cultured with phytohaemagglutinin and culture supernatants assayed for cytokine production. Production of the Th1 cytokines IL-2 and IFN-gamma was low in patients compared to healthy controls, and amounts of these tended to increase after IFN alpha therapy. In two patients high levels of IL-10 were detectable in culture, and these were reduced after IFN alpha. In patients who had high serum concentrations of IL-4 or IL-10, these were also decreased following therapy. Natural killer cell activity, which was low in the patients prior to therapy, was increased following administration of IFN alpha. In those patients with detectable platelet-associated autoantibody to gpIIb/IIIa, the amounts were reduced after treatment. Two patients had an unusually high percentage of T cells expressing the gamma delta T cell receptor, which decreased after therapy. The findings are consistent with an increase in Th 1 activity and a decrease in autoantibody production following IFN alpha therapy, which may be related to the beneficial effects of this cytokine.
Crossley
A R
AR
Dept. of Haematology, University of Newcastle upon Tyne, Medical School.
Dickinson
A M
AM
Proctor
S J
SJ
Calvert
J E
JE
D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000187:drug effects; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism
D001323:Autoantibodies; D016207:Cytokines; D016898:Interferon-alpha; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma