Low-dose IL-2 induces cytokine cascade, eosinophilia, and a transient Th2 shift in melanoma patients

Abstract

Low-dose IL-2 appears to have induced a transient Th2-dominant secondary cytokine cascade at the time of vaccination, for which eosinophilia is a surrogate marker. For future vaccine therapies targeting cytotoxic T-cell responses, delaying IL-2 until after initiation of immune responses may be more effective.

Interleukin-3, Interleukin-5, and Cancer

“…The authors found out that local IL-2 therapy caused significant increase in serum IL-5 levels. Moreover, all the patients developed a marked eosinophilia correlating in magnitude with peak IL-5 serum levels (Cragun et al, 2005). Furthermore, similar findings were obtained by Cragun et al (2005).…”

Group 2 ILCs: A way of enhancing immune protection against human helminths?

“…IL‐2 therapy has a long history in antitumour therapy, and therapies with low‐dose IL‐2 are currently tested in autoimmune disease such as hepatitis C virus‐related vasculitis and type 1 diabetes . Early on, it has been recognized that IL‐2 therapy can lead to increased plasma levels of IL‐5 and eosinophila an effect that, at least in mouse models, is caused by an activation of ILC2s . Side effects of low doses of IL‐2 are considered to be relatively safe, but in the context of autoimmune diseases are used to expand regulatory T cells (reviewed in), which may contradict attempts to trigger a protective response in helminth infections.…”

Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma

“…Several papers look at the ratio of IFN‐γ compared with IL‐5 26 and IL‐4 27,28 as a measure of the Th1/Th2 ratio in patients. We observed an increase in both the IFN‐γ/IL‐5 and IFN‐γ/IL‐4 ratios in half of our patients over the treatment course which would support a shift in the Th1/Th2 ratio to a predominance of Th1 cells, a finding that has been reported to be a good prognostic factor in patients with metastatic renal cell carcinoma and melanoma 37 .…”

“…Using this technique we could assess the functionality of any increases in cell populations being observed. As mentioned above, IFN‐γ is increased in patients with regressing tumours due to the increase in their Th1 responses; 5 additionally, the ratios of IFN‐γ to IL‐4 and IL‐5 have been used as indicators of the Th1/Th2 ratio in patients with malignancy 26–28 . Our investigation aims to determine the production of IFN‐γ from patients’ PBMC over the treatment course along with a comparison of their IFN‐γ/IL‐5 and IFN‐γ/IL‐4 ratios during treatment.…”