In Vitro Interleukin-8 Production by Monocytes Treated with Lithium Chloride from Breast Cancer Patients

Abstract

Aims and background Since interleukin-8 (IL-8) has a suppressive effect on hematopoiesis, lithium induces leukocytosis and granulocytosis and mononuclear cells are defective in patients affected by neoplastic disease, we analyzed IL-8 production by monocytes obtained from patients with non-metastatic breast cancer (BCaMO) and metastatic breast cancer (BCaM1) and the effect of lithium chloride (LiCI) on these cells. Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer and acute leukemia. Lithium influences the hematopoietic system, which is known to be regulated by numerous cytokines including IL-8. Methods We selected three groups of subjects (15 per group): patients affected by BCaMO, BCaM1 and healthy donors (HD) matched for sex and age. IL-8 release was assessed in supernatants of lipopolysaccharide (LPS) and/or LiCI-treated monocyte cultures. Results Monocytes from BCaM1 released higher IL-8 levels than monocytes from BCaMO (P <0.0001); the IL-8 levels of both groups were significantly higher (P <0.0001) than those of HD. In vitro LiCI treatment reduced IL-8 production by monocytes obtained from all subjects compared to the same cells when untreated or LPS treated. The suppressive effect of LiCI on IL-8 production by monocytes from breast cancer patients was particularly marked in monocytes from BCaMO with respect to those from BCaM1. LPS treatment increased the IL-8 production more in BCaM1 monocytes than in BCaMO monocytes. Moreover, combined LPS/LiCI treatment of monocytes significantly (P <0.0001) downregulated 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 BCaMO 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 system in vivo observed following lithium therapy could reside, at least in part, in the ability of lithium to downregulate this chemokine.