Current status and challenges of cytokine pharmacology

Abstract

The major concern of pharmacology about cytokines has originated from plentiful data showing association between gross changes in their production and pathophysiological processes. Despite the enigmatic role of cytokines in diseases, a number of them have become a subject of cytokine and anti-cytokine immunotherapies. Production of cytokines can be influenced by many endogenous and exogenous stimuli including drugs. Cells of the immune system, such as macrophages and lymphocytes, are richly endowed with receptors for the mediators of physiological functions, such as biogenic amines, adenosine, prostanoids, steroids, etc. Drugs, agonists or antagonists of these receptors can directly or indirectly up-and down-regulate secretion of cytokines and expression of cytokine receptors. Vice versa, cytokines interfere with drug pharmacokinetics and pharmacodynamics through the interactions with cytochrome P450 and multiple drug resistance proteins. The aim of the review is to encourage more intensive studies in these fields of cytokine pharmacology. It also outlines major areas of searching promising candidates for immunotherapeutic interventions.

Cytokines and their Role in Health and Disease: A Brief Overview

“…IL-10, IL-11, anti-IL-12, anti-TNF-α are used for the prevention of psoriasis. Cytokines which are antiinflammatory in nature, like IL-10 and IL-11, are used in Crohn's disease and ulcerative colitis [2]. Treatment with altrakincept, a recombinant human soluble IL-4 receptor, neutralizes endogenously produced IL-4 in bronchial asthma patients [43].…”

“…Disease Targets IFN-α Hepatitis B and C [5] IFN-β Multiple sclerosis [5] IFN-γ Chronic granulomatous disease [38], Crohn's disease [65], Multidrug resistant tuberculosis [42] TNF-α Rheumatoid arthritis [30,31], Sepsis [32], Refractory asthma [33], Psoriasis [2] G-CSF Idiopathic neutropenia, Congenital neutropenia, Febrile neutropenia, Leukemic neutropenia, Aplastic neutropenia [37], Bone marrow suppression [5] GM-CSF Bone marrow suppression, Crohn's disease [5] IL-2 Metastatic melanoma, Renal cell carcinoma [46] IL-4 Asthma [43] IL-5 Asthma [44] IL-6 Rheumatic diseases [34] IL-10 Crohn's disease, Ulcerative colitis [2], Psoriasis, Rheumatoid arthritis [5] IL-11 Crohn's disease, Ulcerative colitis, Psoriasis, Rheumatoid arthritis [2] IL-13 Asthma [2,45] Erythropoietin Anaemia, Bone marrow failure [5] HER2-Specific Monoclonal Antibody Adenocarcinoma of stomach, Breast cancer [35,36] …”

“…Treg cells type 1 (Tr1) secrete mainly IL-10and IFN-γ, IL-5 in lesser amount and very low level of TGF-β and IL-2. Tr3 subset of Treg (also called Th3 cells) produces preferentially TGF-β and lesser amounts of IL-10 [2]. According to their secretion they are classified into lymphokines (cytokines that are secreted by T cells and regulate the immune response), proinflammatory cytokines (cytokines that amplify and perpetuate the inflammatory process), growth factors (cytokines that promote cell survival and result in structural changes in the airways), chemokines (cytokines that are chemotactic for inflammatory cells) and anti-inflammatory cytokines (cytokines that negatively modulate the inflammatory response) [3].…”

Virulence genes and cytokine profile in systemic murineCampylobacter coliinfection

“…In addition, its relationship with some pro-inflammatory cytokines is important for the outcome of infection and sepsis. 48 In the present study, the first cytokine that began to rise in the liver of the infected mice was IL-10. C. coli 26536 induced the strongest anti-inflammatory IL-10 response in the liver by the last day of infection (day 8).…”

“…43 Furthermore, the immune functions of cytokines result from the coordinated action of T cells, macrophages and dendritic cells, and these largely depend on the recruitment of these calls to the sites of infection and inflammation, and to other pathological lesions. 48 Previously, Hu et al (2006) 49 demonstrated that C. jejuni infection can trigger innate inflammatory responses, and induce human dendritic cell maturation and production of pro-inflammatory cytokines, including IL-6, IL-8, IL-12 and TNF-a. In this way, cytokines can induce Campylobacter-specific Th1 effector-cell responses, and contribute to the pathogenesis and clinical symptoms of Campylobacter spp.…”