In vitro interleukin-8 production by monocytes treated with lithium chloride from breast cancer patients

Aims and background: Since interleukin-8 (IL-8) has a suppressive effect on hematopoiesis, lithium induces leukocytosis and granulocytosis and mononuc lear cells are defective in patients affected by neoplastic disease, we ana lyzed IL-8 production by monocytes obtained from patients with nonmetastati c breast cancer (BCaM0) and metastatic breast cancer (BCaM1) and the effect of lithium chloride (LiCl) on these cells. Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chem otherapy for cancer and acute leukemia. Lithium influences the hematopoieti c system, which is known to be regulated by numerous cytokines including IL -8. Methods: We selected three groups of subjects (15 per group): patients affe cted by BCaM0, BCaM1 and healthy donors (HD) matched for sex and age. IL-8 release was assessed in supernatants of lipopolysaccharide (LPS) and/or LiC l-treated monocyte cultures. Results: Monocytes from BCaM1 released higher IL-8 levels than monocytes fr om BCaM0 (P<0.0001); the IL-8 revels of both groups were significantly high er (P<0.0001) than those of HD, In vitro LiCl treatment reduced IL-8 produc tion by monocytes obtained from all subjects compared to the same cells whe n untreated or LPS treated. The suppressive effect of LiCl on IL-8 producti on by monocytes from breast cancer patients was particularly marked in mono cytes from BCaM0 with respect to those from BCaM1, LPS treatment increased the IL-8 production more in BCaM1 monocytes than in BCaM0 monocytes, Moreov er, combined LPS/LiCl treatment of monocytes significantly (P<0.0001) downr egulated the release of IL-8 compared to treatment with LPS alone. Conclusions: Our data demonstrate that monocytes from BCaM1 release larger amounts of IL-8 than monocytes from BCaM0 and from HD. Lithium was able to downregulate IL-8 production by monocytes from different subgroups, Further studies are needed to clarify if the improvement of the hematopoietic syst em in vivo observed following lithium therapy could reside, at least in par t, in the ability of lithium to downregulate this chemokine.