Autocrine Cytokines

Pathogenetically relevant cytokines produced by HCs and their autocrine and paracrine effects are summarized in Table 29.6. Among these, TNF, IL-6 and GM-CSF have been reported to promote HC survival/prolif-eration,25-27 while GM- and M-CSF affect malignant-cell adhesion / motility.28 29 HCs also produce bFGF, TGFp, and IL-10, which are involved in processes by which HCs modify extracellular and cellular components of their microenvironment. Thus, bFGF and TGFp are respectively involved in the stimulation of FN production by HCs and of collagen by fibroblasts.3031 Moreover, TGFp can inhibit normal hematopoiesis and also, together with IL-10, suppress the immune functions of T cells and monocytes.3233

In addition to responding to autocrine cytokines, HCs possess a number of receptors for cytokines produced by other cells. Thus, IL-1 is known to upregulate the surface expression of Ig and PCA-1 antigen by HCs,34 while IL-4 and IL-15, alone or in synergy with other growth factors, stimulate the cells to synthesize DNA.35 HCs also possess IL-2 and IL-3 receptors;

expression of the IL-2 receptor (CD25) is of diagnostic importance, but no functional effects of either IL-2 or IL-3 have so far been demonstrated.

In summary, cytokines play a part in most, if not all, pathogenetically important reactions of HCs, including their clonal expansion, their distinctive tissue homing and their influence on both cellular and extracellular components of the invaded tissues. This ultimately results in the suppression of both normal hematopoiesis and immunity—the two most damaging aspects of the disease.

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