The role of cytokines in haematopoiesis.

Cytokines, by definition, exert an effect on haematopoiesis. Diseases characterized by haematopoietic insufficiency, such as aplastic anaemia, should therefore be investigated for abnormal expression of these regulatory proteins. In studies on hairy cell leukaemia, a severe deficiency was found in the production of interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte CSF, IL-6 and tumour necrosis factor alpha (TNF alpha). Further studies on IL-6 at the mRNA and protein levels revealed that peripheral blood mononuclear cells and even hairy cells could be stimulated by interferon alpha (IFN alpha) to produce IL-6. It is interesting to speculate on the beneficial effects of IFN alpha therapy on the expansion of normal haematopoiesis and suppression or even elimination of malignant cells. Studies on a patient with angio-immunoblastic lymphadenopathy, another disease showing haematopoietic insufficiency, who developed severe aplastic anaemia, showed massive increases in IFN gamma and TNF alpha levels in serum; IL-6 and GM-CSF levels were below the limit of detection. These results correlated with an abnormal distribution of CD4+ and CD8+ T lymphocytes in the patient's blood and were compatible with the suppressive effects of IFN gamma and TNF alpha on haematopoiesis.