Effect of doxorubicin on cytokine production by lymphocytes and the Th1/Th2 balance.

Doxorubicin (DOXO) is a potent chemotherapeutic used mainly against solid tumours; however, it has several side effects that can limit its clinical use. On the other hand, the effect of DOXO upon lymphocyte function is controversial. Some studies demonstrate that DOXO administration in vitro suppresses T-cell activation, while the cellular function has been shown to increase in vitro. The objective of this study was to investigate the effect of DOXO on lymphocyte cytokine production in rats. The animals were divided into: SAL (control, n=10) and DOX (DOXO treated, n=10). The DOX group received only one DOXO dose at 15 kg Kg(-1) by intraperitoneal injection. Forty-eight hours after DOXO administration, the animals were killed by decapitation. IL-2 production was significantly enhanced (p<0.05) in lymphocytes from rats treated with DOXO (169.17 ± 21.73 pg mL 10(5) cell) as compared to cells from SAL (45.92 ± 10.53 pg mL 10(5) cell). The administration of DOXO decreased (<0.05) IL-4 production in the DOXO group (29.85 ± 13.09 pg mL 10(5)cell) relative to the SAL group (75.08 ± 15.31 pg mL 10(5)cell). The IL-2/IL-4 ratio was higher (<0.05) in the DOX group (5.99 ± 0.44), as compared to SAL group (0.73 ± 0.12). In conclusion, our results suggest that a dose of DOXO promotes an alteration in the Th1/Th2 balance, promoting a shift towards a Th1-dominant cytokine response.

Insulin and prostaglandins as signals between tumor and the host immune system

The development of malignant tissue in vivo is partially favored by the immunosuppression that occurs in cancer patients. However, the signals between tumor and immune tissues remain to be identified. We present evidence that prostaglandins may act as one of these signals by a direct action on cells of the immune system, or by inhibition of insulin secretion which in turn suppresses immune function, or both