Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma

Abstract

Transient inflammatory reactions have been reported in a subpopulation of patients with multiple myeloma (MM) during lenalidomide (Len) plus dexamethasone (DEX) therapy. Here, we examined serum levels of Th1 (IL-2 and IFN-γ) and Th2 cytokines (IL-6 and TNF-α) in nine refractory or relapsed MM patients treated with Len plus low-dose DEX. Six patients showed elevation of C-reactive protein (CRP) after the initiation of therapy. In these patients, IFN-γ and IL-6 were also elevated in two and three patients, respectively. The remaining three patients showed no appreciable changes in CRP or these cytokines. Furthermore, Len enhanced the production of both Th1 and Th2 cytokines in normal peripheral blood mononuclear cells and in patient bone marrow mononuclear cells containing primary myeloma cells and lymphocytes. These results suggest that the modulation of the Th1 and Th2 cytokine production by Len may contribute to transient inflammatory reaction in MM patients.

Patient with Refractory Multiple Myeloma Developing Eosinophilia after Lenalidomide Treatment and Lung Cancer 9 Months Later: Case Report and Review of the Literature

“…Richter et al [12] reported that lenalidomide induces eosinophilia through the activation of NK/T cells. In addition, there are reports that human eosinophils produce IL-6 [13] and that many patients with myeloma show increase of the serum IL-6 during treatment with lenalidomide [14]. However, there is also a report of the serum ILb Fig.…”

Inflammatory environment created by fibroblast aggregates induces growth arrest and phenotypic shift of human myeloma cells

“…In general, inflammation is frequently observed in cancer patients receiving treatment modalities with various modes of action. Transient inflammatory reactions have been reported in subgroup of patients with MM during lenalidomide plus dexamethasone therapy [11]. The inflammatory response is characterized by coordinate activation of various signalling pathways including NF-κB in resident tissues [12].…”

Increased serum tumor necrosis factor α levels in patients with lenalidomide-induced hypothyroidism

“…Despite pro-inflammatory cytokine deregulation being postulated as a mechanism of lenalidomide-induced hypothyroidism, pre- and post-treatment serum inflammatory cytokine levels following lenalidomide administration have only been published in one small case series and have not been assessed in relation to the development of hypothyroidism. In a group of six patients with MM and a significant elevation (over 1 mg/dL increase) in C-reactive protein (CRP) after lenalidomide treatment, Harada et al found no significant increase in serum tumor necrosis factor alpha (TNF-α), interferon gamma (IFN- γ ), interleukin-2 (IL-2), or interleukin-6 (IL-6) after therapy[7]…”