Immunomodulation treatment

In conclusion, IFNs have proven to be invaluable tools in the fight against chronic viral hepatitis. In these indications, their antiviral properties play a major role and it remains unclear whether their immunomodulatory properties are also important. Disappointing results obtained with purely immunomodulatory molecules, such as interleukins or Toll-like receptor agonists suggest that, if immunomodulation plays any role, potent inhibition of viral replication is also needed. The role of IFNs in the treatment of viral infections other than hepatitis B and C remains elusive. 

Sarin SK, Sood A, Kumar M, Arora A, Amrapurkar D, Sharma BC, Konar A, Chawla YK, Jain RK, Nanda V, Kumar A, Hissar S, Lavate P, Lahoti D (2007) Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B. Am J Gastroenterol 102 96-104... 

A variety of other clinically important infections, such as brucellosis, listeriosis, salmonellosis, and various Mycobacterium infections, are of interest as these are often localized in organs rich in MPS cells. Liposome encapsulation has been demonstrated to improve therapeutic indices of several drugs in a number of infectious models. The natural avidity of macrophages for liposomes can also be exploited in the application of the vesicles as carriers of immunomodulators to activate these cells to an microbicidal, antiviral, or tumoricidal state. These studies were recently reviewed by Emmen and Storm (1987), Popescu et al. (1987), and Alving (1988). In addition to the treatment of "old" infectious diseases, the concept of MPS-directed drug delivery is of considerable interest for the therapy AIDS, possibly enabling control of human immunodeficiency virus replication in human macrophages. 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

Lenalidomide is an immunomodulating agent related to thalidomide that was recently approved for the treatment of patients with multiple myeloma and myelodysplastic syndrome (MDS). Lenalidomide lacks the common side effects of thalidomide, such as constipation and peripheral neuropathy. Interim analyses of two phase III trials show that lenalidomide in combination with dexamethasone produces higher response rates than dexamethasone alone in relapsed and refractory myeloma. Adverse effects of lenalidomide include diarrhea, nausea, muscle cramps, hematologic side effects and deep vein thrombosis.42... 

Caryophyllidae are an interesting source of oligosaccharides and peptides with potential anti-inflammatory and/or immunomodulating effect. These polar compounds might for instance explain the fact that the fresh juice expressed from Aerva lanata (L.) Juss. (Amaranthaceae) inhibits carrageenan-induced edema in rodent. Note that the seeds of Gomphrena species inhibit the formation of IL-6 by osteoblastic cells (MC3T3-E10) without cytotoxicity in vitro. Such property could be useful for the treatment of chronic rheumatoid arthritis, infection, and cancer. In the Lauraceae, trans-cinnamal-dehyde from Cinnamomum cassia (Lauraceae, order Laurales) inhibits in vitro the... 

Malinowski, E. (2002), The use of some immunomodulators and non-antibiotic drugs in a prophylaxis and treatment of mastitis . Polish Journal of Veterinary Sciences, 5, 197-202. 

D Hooghe TM (2003) Immunomodulators and aromatase inhibitors are they the next generation of treatment for endometriosis Curr Opin Obstet Gynecol 15 ... 

Other studies describe similar beneficial effects for PUFA-enriched diets to treat Crohn s disease, other inflammatory bowel diseases such as ulcerative colitis, as well as psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis [57], Thus, immunomodulation by PUFAs appears to be a promising intervention for the treatment of many autoimmune and inflammatory diseases. 

Cyclosporine is an immunomodulating agent used mainly to inhibit rejection after transplantations and it has a narrow therapeutic interval. Grapefruit juice is a strong inhibitor of the cyclosporine metabolism (CYP 3A4) and increases the blood concentration of cyclosporine. This can lead to toxicity but can also be used to reduce the doses and decrease the costs of the cyclosporine treatment. 

Grunwald MH, Ben Amitai D, Amichai B. (2004) Macrolactam immunomodulators (tacrolimus and pimecrolimus) New horizons in the topical treatment of inflammatory skin diseases. J Dermatol 31 592-602. 

Encapsulation of immunomodulators, e.g. muramyl tripeptide analogues, into liposomes has been designed to stimulate host immunity [108] and can be used in combination with other treatment modalities. The systemic activation of macrophages provides an additional therapeutic modality for the eradication of cancer and cancer metastases. 

Liposome-encapsulated immunomodulators are currently under investigation in different patient groups although this development has certainly not advanced as far as that with the liposomal anthracyclines. MLV-MTP-PE (multilamellar vesicles-muramyl tripeptide-phos-phatidylethanolamine) was studied in several clinical trials in osteosarcoma patients who developed pulmonary metastases during adjuvant chemotherapy [108], The intravenous administration of MLV-MTP-PE induced tumouricidal properties in monocytes as well as increase in serum IL-1 shortly after intravenous infusion. Furthermore elevations in C-reactive protein, 32-microglobulin and ceruloplasmin were frequently observed. Even higher anti-tumour activity was observed in combination with ifosfamide. These preliminary results suggests that liposome-encapsulated immunomodulators in combination with chemotherapy may be an appropriate treatment for recurrent disease. 

Imiquimod is approved for the local treatment of external genital and perianal warts in adults. The agent has immunomodulating effects and it also stimulates antiviral activity. 

ZD6474 is one of the many immunomodulating molecules currently in clinical trials for the treatment of various types of cancers. Its aqueous solubility (330 (xM at pH 7.4) and antitumor activity at a dosage as low as 12.5 mg/kg per day in mice made this compound a good candidate for clinical trials in replacement of the more potent but less bioavaUable analog ZD4190. 

It is an immunomodulator agent used locally in the treatment of external genital perianal warts in adults. 

Investigational agents for the treatment of HCV infection are multiple and include inhibitors of the HCV RNA polymerase such as valopicitabine. Pis such as telaprevir, the ribavirin analogs merimepodib and viramidine, an anti-aminophospholipid antibody, a caspase inhibitor, and the immunomodulator thymosin alpha-1. 

Imiquimod (Aldara) is an immunomodulator approved for the treatment of external genital and perianal warts in adults, actinic keratoses on the face and scalp, and biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities. The mechanism of its action is thought to be related to imiquimod s ability to stimulate peripheral mononuclear cells to release interferon- and to stimulate macrophages to produce interleukins-1, -6, and -8, and tumor necrosis factor- (TNF-k). 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

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