DEFICIENT PRODUCTION OF TUMOR-NECROSIS-FACTOR BY PERIPHERAL-BLOOD MONOCYTES IN CHRONIC LYMPHOCYTIC-LEUKEMIA

The production of tumor necrosis factor (TNF) by lipopolysaccharide (LPS)‐triggered peripheral‐blood mononuclear cells (PBM) was investigated in 23 patients with untreated B‐cell chronic lymphocytic leukemia (B‐CLL) and 14 control donors. Cells were stimulated at concentrations that reflect cell density in peripheral blood. Under these conditions, PBM from 11/23 of the CLL patients produced at least 10‐fold less TNF as compared with controls. Monocyte numbers were decreased in percentage, while absolute numbers (normal range 233 ± 120 × 103/mm3) were decreased only in 2, normal in 17 and increased in 4 patients indicating that the deficiency is not a result of monocytopenia in most patients. Cell separation experiments indicate that after removal of leukemic B cells, percentages of monocytes return to control range and TNF production is improved (7/7). In mixing experiments, we found a suppression of TNF production in control mononuclear cells by CLL cell samples (75 × 106 cells/ml) in 5/19 cases, while control cells from thymus exhibited no or little suppression in these conditions. In 2‐chamber experiments, leukemic samples suppress TNF production by normal monocytes across a 0.45μm membrane indicating that a soluble factor is responsible for suppression. The factor exhibits higher stability in serum‐free conditions and its molecular weight is below 20kDa. Prostaglandins are not involved, since indomethacin did not abrogate suppression. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company