Altered release of tumor necrosis factor and its soluble receptor in non-Hodgkin's lymphoma patients

Increased expression and elevated serum levels of tumor necrosis factor-alp ha (TNF-alpha) have been shown to be associated with the presence of consti tutional B symptoms and poor prognosis in non-Hodgkin's lymphoma (NHL) pati ents. Soluble TNF receptors (sTNF-R) are suggested to act as biological buf fers in inflammatory conditions by binding and inactivating increased circu lating TNF. Whereas studies have shown elevated TNF to be correlated with B symptoms, similar studies showing the status of soluble receptor release i n these patients have not been conducted. Here, we show that there is incre ased soluble p75 TNF receptor release from peripheral blood mononuclear cel ls (PBMNC) in NHL patients in the early stages of the disease but it is sev erely depressed in patients with advanced disease. Decreased release is ass ociated with presence of B symptoms in these patients. All NHL patients als o show increased TNF secretion and a decreased rate of receptor release wit h time compared with healthy controls. These findings imply that decreased sTNF-R receptor release, in addition to increased TNF secretion, is also im portant in predisposing the patients to B symptoms. This opens up the possi bility of the use of sTNF-Rs as a therapeutic tool to counter increased TNF and alleviate systemic symptoms in these patients and also as a marker for the progression of the disease.