Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases

Abstract

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

Potentiation by cigarette smoke of macrophage function against Leishmania donovani infection

“…Congruent to this idea, we have shown that a treatment with NAC, a known antioxidant, reverses the effect of CSE on infected macrophage and restricts CSE-induced reduction of parasite burden. The interplay between Th1 and Th2 cytokines is very critical in determining the host defense [34]. Th1 cytokines induce cell mediated immune response, activate macrophage, and thus provides resistance to infection.…”

BCG response prediction with cytokine gene variants and bladder cancer: where we are?

“…Interleukin-4 also inhibits macrophage activation and might be involved in cancer formation. IL-4 is a growth co-stimulator for B and T cells, mast cells, erythroid progenitors, and myeloid progenitors that favor a strong humoral immune response (Lucey et al 1996). Many studies have conWrmed that cancer patients have high levels of Th2 cytokines such as IL-10 and IL-6 including IL-4 (Sosroseno et al 1994;Chandler et al 2002).…”

The Immune System in Cancer: If It Isn't Broken, Can We Fix It?

“…10.5A) [23]. In animal models of autoimmune disease, the injection of adjuvants (see Appendix) is usually necessary [24] ± and sometimes sufficient [25,26] ± to induce the pathology.…”

“…In particular, genes affecting T cell recognition of peptides (e. g. specific MHC haplotypes) are often central to the development of autoimmune disease [15,20,22]. Finally, the mechanisms that promote the unintentional turning of the immune system against self targets also means that it might be possible to copy these mechanisms to enhance the immunogenicity of self or near-self tumor antigens [23]. So, it might be possible to use the initiating agents for autoimmune disease [24±27, 30] as adjuvants in immunotherapy.…”