Immunomodulation cytokines

Immunomodulators are a group of mostly stimulatory effectors which act on cells of the immune system (e.g. cytokines, interferons). 

SCOTT F W, ROWSELL P, WANG G S, BURGHARDT K, KOLB H, FLOHE S (2002) Oral exposure tO diabetes-promoting food or immunomodulators in neonates alters gut cytokines and diabetes. Diabetes. 51 73-8. 

Bone metabolism has quickly become a topic of fascinating research. The bone, far from being a metabolically inactive tissue, is a tissue where different cell types and different molecules carry out numerous and varied functions. This has been due largely to the discovery of the RANKL/RANK/OPG system of cytokines. These new molecules are decisive in OCS, bone metabolism, and bone loss, but they are also important for other tissues and cells. Indeed, these proteins are critical in several systems the immune system, where they have functions that affect cell survival and the immunomodulation of T-, B-, and dendritic cells the vascular system and the endocrine system. 

Cells of the T cell lineage appear to be more sensitive to the immunomodulatory effects of Pb compared to other lymphoid populations. In addition, there are considerable differences in sensitivity across various T cell subpopulations [38 41], This differential sensitivity has become another major hallmark of Pb-induced immunotoxicity, although most data implicate T cells as indirect targets of Pb immunotoxicity. Both in vivo and in vitro observations of T-dependent immune responses in the presence of Pb suggest that T helper function and Th-dependent cytokines are skewed preferentially toward Th2 reactivities. Smith and Lawrence [42] found that Pb inhibited antigen presentation and stimulated a T cell clone of the Thl phenotype. McCabe and Lawrence [38] were the first to show that Pb inhibited Thl stimulation while it promoted presentation to Th2 clones. Heo and colleagues [39 41] provided both in vitro and in vivo results supporting this immunomodulation by Pb. 

Cytokines, growth factors, enzymes, immunomodulators, and thrombolytics... 

An exciting application of immunomodulating therapy is in the use of cytokines lymphokines, monokines). As mentioned earlier in this chapter, immune cell function is regulated by cytokines produced by leukocytes or other supporting cells. With the advent of genetic engineering, cytokines can be produced in pure form and in large quantities. 

Mechanism of Action An immunomodulator that inhibits release of cytokine, an enzyme that produces an inflammatory reaction. Therapeutic Effect Produces anti-inflammatory activity. 

Given the importance of immunomodulators, this is a drug design area that is too important to be left to the vagaries of serendipity. The cytokines represent the best hope for rational drug design in the area of immunomodulation. 

Figure 6.3 A vast array of chemical mediators influence immunomodulation and cellular growth. These various mediators are linked to one another. For example, interferons are a subset of cytokines, which in turn are a subset of growth factors.

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

Immunomodulators (nonvaccine, nonallergenic) Growth factors, cytokines, some hormones and monoclonal antibodies intended to mobilize, stimulate, decrease, or otherwise alter the production of hematopoietic cells in vivo... 

Tomkins WA (1999) Immunomodulation and therapeutic effects of the oral use of interferon-alpha mechanism of action. J Interferon Cytokine Res 19 817-828. 

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