Interferon Production and Lymphocyte Transformation in Lymphocytes of Leukemic Patients

Abstract

The high incidence of viral infections in patients with lymphocytic leukemia is well documented, but the role played by interferon in the pathogenesis of such infections is not known. In this study, we investigated the possibility that gamma (gamma) interferon production, induced by phytohemagglutinin (PHA) might be impaired in leukocytes from patients with acute lymphocytic leukemia (ALL). We also compared this response with alpha (alpha) interferon production, and with PHA-stimulated lymphocyte transformation. We have shown that the gamma interferon response of leukocytes from patients, both in relapse and in remission, was markedly lower than in leukocytes from normal donors. However, the alpha interferon response in leukocytes from the patients was normal. In contrast the defective gamma interferon response to PHA stimulation of cells from patients in remission, lymphocyte transformation by PHA was normal. Lymphocytes from patients in relapse has a delayed response. Our findings suggest (1) that the defective gamma interferon response which occurs in cells from patients with ALL, both in relapse and remission, contributes to increased susceptibility to viral infections, (2) that alpha interferon may not be the optimal type of interferon for treatment of certain viral infections, and (3) that different triggering mechanisms, or different receptors, exist for PHA-induced gamma interferon production and for lymphocyte transformation in cells of patients with ALL.

Interferon responses of peripheral blood mononuclear cells from normal and leukaemic children

“…However, these results contradict the three most recent reports of virus induced interferon alpha production in PBMC of ALL patients where only slightly reduced levels were reported after 1 8 h stimulation (Strander et al, 1970: Chisholm & Cartwright, 1978: Lazar et al, 1981. However, these results contradict the three most recent reports of virus induced interferon alpha production in PBMC of ALL patients where only slightly reduced levels were reported after 1 8 h stimulation (Strander et al, 1970: Chisholm & Cartwright, 1978: Lazar et al, 1981.…”

“…At 18-24 h poststimulation any residual inducing virus must be inactivated before interferon assay and this has generally been accomplished by lowering the pH of the culture supernatants to pH 2 (Lee et al 1969;Strander et al 1970;Chisholm & Cartwright, 1978;Lazar et al, 1981). At 18-24 h poststimulation any residual inducing virus must be inactivated before interferon assay and this has generally been accomplished by lowering the pH of the culture supernatants to pH 2 (Lee et al 1969;Strander et al 1970;Chisholm & Cartwright, 1978;Lazar et al, 1981).…”

“…although later studies have failed to confirm this (Strander et al, 1970;Chisholm & Cartwright. 1978;Lazar et al, 1981). In PBMC, alpha interferons, the major sub-types of which are heat and pH stable, are secreted predominantly by monocytes (Friedman & Vogel, 1983).…”

“…To date, the methods employed in viral stimulation of PBMC from children with leukaemia have precluded the induction and/or assay or acid labile forms of interferon. A defect of interferon gamma production on stimulation of ALL PBMC with mitogens has, however, been reported (Lazar et al, 1981).…”

“…In PBMC, alpha interferons, the major sub-types of which are heat and pH stable, are secreted predominantly by monocytes (Friedman & Vogel, 1983). A defect of interferon gamma production on stimulation of ALL PBMC with mitogens has, however, been reported (Lazar et al, 1981). To date, the methods employed in viral stimulation of PBMC from children with leukaemia have precluded the induction and/or assay or acid labile forms of interferon.…”