Inflammatory Cytokine Pattern Is Sex-Dependent in Mouse Cutaneous Melanoma Experimental Model

Abstract

We present the evaluation of inflammatory cytokines in mouse cutaneous melanoma experimental model, as markers of disease evolution. Moreover, to test our experimental model, we have used low doses of dacarbazine (DTIC). C57 BL/6J mouse of both sexes were subjected to experimental cutaneous melanoma and treated with low doses of DTIC. Clinical parameters and serum cytokines were followed during tumor evolution and during DTIC therapy. Cytokine/chemokine pattern was assessed using xMAP technology and the following molecules were quantified: interleukins (IL)-1-beta, IL-6, IL-10, IL-12 (p70), interferon (IFN)-gamma, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP-1), and keratinocyte-derived chemokine (KC). Significant differences were found between normal females and males mice, female mice having a statistically higher serum concentration of IL-1-beta compared to male mice, while males have a significantly higher concentration of MIP-1-alpha. During melanoma evolution in the female group, IL-1-beta, MIP-1-alpha, and KC circulatory levels were found 10-fold increased, while other cytokines doubled their values. In the male mice group, only circulatory KC increased 4 times, while IL-1-beta and TNF-alpha doubled their circulatory values. Various serum cytokines correlated with the disease evolution in cutaneous melanoma mouse model.

In the mix: the potential benefits of adding GM-CSF to CpG-B in the local treatment of patients with early-stage melanoma

“…20 Moreover, a sex-dependent inflammatory cytokine pattern during melanoma development was also described before in an experimental mouse model. 21 Improved pDC activation and IFNα release by GM-CSF has also been previously reported, 22 but, as far as we know, has never previously been linked to sex-dependent mechanisms. It is important to note that despite these remarkable differences in DC subset activation, we did not find any differences in RFS between women receiving CpG-B only or CpG-B combined with GM-CSF.…”

Mediators of Inflammation – A Potential Source of Biomarkers in Oral Squamous Cell Carcinoma

“…It has been shown to be involved in processes such as inflammation, immune response control, hematopoiesis, and oncogenesis. However, under certain conditions, elevated levels of IL-6 may lead to disturbances of the immune response [ 71 , 73 – 75 ]. IL-6 can induce the transition from acute to chronic inflammation by recruiting monocytes to the site of inflammation through monocyte chemoattractant protein-1 (MCP-1) secretion [ 76 ].…”

A new clinical tool to predict outcome in early-stage melanoma patients

“…Most of these cells secrete cytokines that may play a key role in inhibiting or promoting tumor progression 35 . The proinflammatory cytokines IL-4 and IL-6, produced either by host immune cells or tumor cells themselves, are associated with tumor malignancy in patients and animal cancer models 36,37,38 . At the cutaneous level, keratinocytes secrete IL-6 in order to enhance T cell-mediated antitumor activity and therefore, high IL-6 levels are considered a marker for immune system upregulation 37,38 .…”

“…The proinflammatory cytokines IL-4 and IL-6, produced either by host immune cells or tumor cells themselves, are associated with tumor malignancy in patients and animal cancer models 36,37,38 . At the cutaneous level, keratinocytes secrete IL-6 in order to enhance T cell-mediated antitumor activity and therefore, high IL-6 levels are considered a marker for immune system upregulation 37,38 . IL-4 is the most important Th2 cytokine, and it is mainly produced by activated T cells, mast cells, basophils and eosinophils in order to regulate lymphocyte proliferation and survival 37 .…”