Immunomodulatory actions

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

Interferons a-2b (Intron-A), a-nl, and a-n3 (Alferon N) have both intrinsic antiviral effects and antiproliferative and immunomodulatory actions. These interferons are approved for intralesional therapy of refractory or recurrent condylomata (genital warts). Toxicities include flulike symptoms, nausea, depression of the white blood cell count, and mild diminution in hematocrit. 

Previously, in the early 1980s (Figure 16.22) it was proved that the G115 extract exerts immunomodulatory actions in animals. Singh et al.15-16 demonstrated that G115 protects... 

As well as their core intracellular activities, many annexins have evolved other, specialised extracellular functions, such as the immunomodulatory action of annexin 1 or the pro-fibrinolytic activity of annexin 2. In this guise they contribute to homeostasis and repair regulating and resolving infection and trauma, and will doubtless prove to be involved in many pathological processes. In the case of autoimmunity, when these mechanisms become disturbed, annexins are again implicated (for example in APL, SLE and diabetes) which underscores their importance as key regulatory factors. 

At an advanced stage (II, III) with AMA profile B, the combination of UDCA -I- prednisolone (maintenance dose 4-8 mg/day in the morning) should generally be administered as first medication. In the case of unsatisfactory therapeutic results or with AMA profiles C or D (= stages III or IV), we would recommend the additional administration of azathloprine as a triple therapy. A dosage of 1 x 50 mg (up to 2 x 50 mg) per day is well-tolerated and, like prednisolone at this dosage, has relatively few side effects. A maintenance dose of 50 mg every second day may be sufficient. (170) The immunomodulatory action of UDCA is thus combined with the immunosuppressive effect of azathioprine, while the antiinflammatory characteristics of the steroids are also included, i.e. the two-substance combination is extended to a triple combination if necessary, especially in profiles Cor D. 

A77 1726 inhibits dihydro-rate dehydrogenase, the rate-limiting enzyme in pyrimidine synthesis. It inhibits the proliferation of T and B cells, and probably acts via the production and action of interleukin-2. Besides its immunomodulatory action, A77 1726 also has an antiinflammatory action by inhibition of nuclear factor kappa B (NFkB), tumor necrosis factor alfa (TNF-a),... 

Penicillamine often elicits multiple adverse reactions in the same patient, illustrating its immunomodulatory actions. Examples are listed in Table 4. 

Roxithromycin had an immunomodulatory action on peripheral blood mononuclear cells in patients with psoriasis (13). The anti-inflammatory activity of roxithromycin is due to reduced production of proinflammatory mediators, cytokines, and co-stimulatory molecules, as has been shown in animal studies (14). 

Since its withdrawal, thalidomide has been found to be effective in the treatment of erythema nodosum lepro-sum, and in 1997 it was marketed in the USA for this indication. The mechanism of action of thalidomide is stiU unclear (1,2), but it has many anti-inflammatory and immunomodulatory actions in vitro and in vivo (3,4). 

The immunomodulatory action of glycosides from Cucumaria japonica has an applied significance because the glycoside Ifaction from Cucumaria japonica is not mutagenic [27]. These glycosides were approved for veterinary use in Russia [103]. 

Immunomodulatory action of sea cucumber glycosides at very low concentrations has the greatest interest from the pharmacological point of view. It reasonable, that this action is also related to the modifying effect on membranes of target cells. 

Juge-Aubry CE, Meier CA. Immunomodulatory actions of leptin. Molec Cell Endocrinol 2002 194 1-7. 

Usha D (1995) Immunomodulatory actions of Tinospora cordifolia. A dissertation for the M.D. examination University of Bombay... 

The polysaccharide isolated from B. kummingense showed an immunomodulatory action on the proliferative response of mouse splenocytes to mitogens as measured by H-thymidine incoporation [24]. 

Perez-Cano FJ, Franch A, Castellote C, CasteU M (2003) Immunomodulatory action of spermine and spermidine on NR8383 macrophage line in various culture conditions. CeU Immunol 226 86-94... 

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