Chemokines and Stealth Viruses:A Blueprint for Therapy in Infected Humans and Animals (Part II)













Continued from Part I

Partial Listing of Agents Known to Influence Chemokine Production and Activities

The accompanying table is intended to illustrate the vast number of agents that have been reported to influence the production and/or activities of CC and CXC chemokines. The cytokine NF-kB is a potent stimulus to chemokine production. NF-kB is normally maintained in an inactive state due to inhibitory molecules. Activation can occur due to the production of TNF and other cytokines. In turn, TNF production can be evoked by various factors, including oxidative stresses. Chemokine production can be regulated, therefore, by agents that act at various levels, including suppressing the production of oxygen free radicals with antioxidants, suppressing TNF and/or NF-kB production, directly acting on chemokine production or interfering with the production and/or activity of chemokine receptors. Activation of certain other pathways can lead to inhibition of chemokine production, for example prostaglandin E (2), interleukin 10 and their inducing agents can down regulate chemokine synthesis. Several compounds can have opposing actions, depending on dose, cell type and inducing stimulus.


Therapeutic Approaches Aimed at Supression of Cytokine/Chemokine Mediated Stealth Virus Infection

Legend:

* The use of these medications solely for stealth virus infections is not being suggested. This does not, however, preclude an assessment of their potential anti-stealth virus activity in patients in whom the use of the medication is medically indicated.
+ ACE Angiotension converting enzyme
# Cholesterol lowering

Therapeutic agents and the reference to its effect on cytokine/chemokine mediated activities:

Antioxidants:

  • Vitamin C (Vlahopoulos S, et.al. Blood 1999;94:1878-89)
  • Vitamin E (Wu D, et.al. Atherosclerosis. 1999; 7:297-307)
  • N-acetyl-cysteine (Gosset P, et.al. Eur Respir J 1999;14:98-105)
  • Alpha-lipoic acid (Suzuki YJ, et.al. Biochem Biophys Res Commun 1992;189:1709-15)
  • Coenzyme Q10 (Hodges S, et.al. Biofactors 1999;9:365-70)
  • Butylated hydroxytoluene BHT (Hulten LM, et al. Transplantation 1998;66(3):364-9)

Diet and nutritional supplements:

  • Asparagus cochinchinensis (Kim H, et al. Int J Immunopharmacol 1998;20(4-5):153-62)
  • Gamma linoleic acid (Dirks J, et.al. Prostaglandins Leukot Essent Fatty Acids 1998;59:273-7)
  • Omega-3 lipids (Venkatraman JT andChu WC . J Am Coll Nutr 1999;18:602-13)
  • Fish oil (James MJ, et al. Am J Clin Nutr 2000;71(1 Suppl):343S-8S)
  • Flaxseed oil (James MJ, et al. Am J Clin Nutr 2000;71(1 Suppl):343S-8S)
  • Palm oil (Engelberts I, et.al. Br J Nutr 1993;69:159-67)
  • Fiber (Andoh A, et.al. JPEN J Parenter Enteral Nutr 1999;23(5 Suppl):S70-3)
  • Butyrate (Andoh A et al. Clin Exp Immunol 1999;118:23-9)
  • Yogurt (Ha CL, et.al. J Food Prot 1999;62:181-8)
  • L-Glycine (Spittler A, et al. FASEB J 1999 ;13:563-71)
  • L-Arginine (Haberstroh U, et al. J Am Soc Nephrol 1998 ;9:203-10)
  • Zinc (Connell P, et al. J Am Coll Nutr 1997 ;16:411-7)
  • Inosine (Hasko G, et al. J Immunol 2000;164:1013-9)
  • Taurine chloramine (Kontny E, et al. Arthritis Rheum 1999;42:2552-60)
  • S-adenosylmethionine (Watson WH, et al. Biochem J 1999;342 ( Pt 1):21-5)
  • DHEA (Araghi-Niknam M, et al. Proc Soc Exp Biol Med 1997 ;216:386-91)

Herbal medicines:

  • Bindarit (Zoja C, et al. Kidney Int 1998 ;53:726-34)
  • Capsaicin (Yu R, et al. Int J Vitam Nutr Res 1998;68:114-9)
  • Curcumin (Jobin C, et al.. J Immunol 1999;163:3474-83)
  • Chongmyung-Tang (Kim HM, et al. J Ethnopharmacol 1999;66:295-300)
  • Epigallocatechin gallate (Yang F, et al. J Nutr 1998;128:2334-40)
  • Cimicifuga rhizoma (Hirabayashi T, et al.. Planta Med 1995;61:221-6)
  • Genistein (Tabary O, et al. Am J Pathol 1999;155:473-81)
  • Ginkgo biloba (Wei Z, et al.. Gen Pharmacol 1999;33:369-75)
  • Hymenialdisine (Breton JJ, et al. J Pharmacol Exp Ther 1997;282:459-66)
  • Oren-gedoku-to (Wang LM,et al.. J Pharm Pharmacol 1997;49:102-4)
  • Polygala tenuifolia (Kim HM, et al.. J Ethnopharmacol 1998;61:201-8)
  • Rosmarinus officinalis (Linn al-Sereiti MR, et al. Indian J Exp Biol 1999;37:124-30)
  • Glucosidorum Tripterygii tororum (Wang ZG. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1997;17:348-50)
  • Quercetin (Ishikawa Y, et al. J Am Soc Nephrol 1999;10:2290-6)
  • Rehmannia glutinosa (Kim HM,. et al. Pharmacol Res 1999;40:171-6)
  • Gallic acid esters (red wine) (Murase T, et al. Arterioscler Thromb Vasc Biol 1999;19:1412-20)
  • Sanguinarine (Chaturvedi MM, et al. J Biol Chem 1997;272:30129-34)
  • Sesquiterpene lactone helenalin (Lyss G, et al. J Biol Chem 1998;273:33508-16)
  • Silymarin (Saliou C, et al. FEBS Lett 1998;440:8-12)
  • Urtica dioica (Riehemann K, et al. FEBS Lett 1999; 8;442:89-94)
  • Zingiberaceae (Surh Y. Mutat Res 1999;428:305-27)

Anti-leukotriene medications:

  • Montelukast (Denizot Y, et al. Cytokine 1999;11:606-10)
  • Zileuton (Aoki Y, et al. Am J Physiol 1998;274:L1030-9)

Over the Counter anti-ulcer medications:

  • Sulglycotide (Slomiany BL, Piotrowski J, Slomiany A. J. Physiol Pharmacol 1997;48:345-51)
  • Rebamipide (Aihara M, et al.. Dig Dis Sci 1998;43(9 Suppl):174S-180S)
  • Polaprezinc (Shimada T, et al.. J Pharmacol Exp Ther 1999;291:345-52)

Over the counter anti-rheumatic medications:

  • Aspirin (Shi X, et al. Mol Cell Biochem 1999;199:93-102)
  • Ibuprofen (Stuhlmeier KM, et al. Biochem Pharmacol 1999 1;57:313-20)
  • Sodium salicylate (Lemay S, et al. Clin Diagn Lab Immunol 1999;6:567-72)
  • Nimesulide (Azab A, et al. J. Life Sci 1998;63: 323-7)
  • Diclofenac (Henrotin YE, et al. Clin Exp Rheumatol 1999;17:151-60)

Prescription anti-rheumatic drugs*:

  • Chloroquine (Zhu X, et al.. Immunology 1993;80:122-6)
  • Sulfasalazine (Deleuran B, et al. Cytokine 1992;4:403-9)
  • D-penicillamine (Deleuran B, et al. Cytokine 1992;4:403-9)
  • Gold (Yoshida S, et al. Int Immunol 1999;11:151-8)
  • Glucocorticoids (Bourke E, and Moynagh PN. J Immunol 1999;163:2113-9)
  • Methotrexate (Boiardi L, et al. Clin Exp Rheumatol 1999;17:419-25)
  • Bucillamine (Matsuno H, et al.. Int J Immunopharmacol 1998;20:295-304)
  • Quinine (Maruyama N, et al. Am J Respir Cell Mol Biol 1994;10:514-20)
  • Quinacrine (Bondeson J, and Sundler R. Gen Pharmacol 1998;30:357-66)
  • Thalidomide (Dunzendorfer S, et al. Immunopharmacology 1999;43:59-64)

Antibiotics that suppress chemokines*:

  • Clarithromycin (Matsuoka N, et al. Clin Exp Immunol 1996;104:501-8)
  • Roxithromycin (Nonaka M, et al. Acta Otolaryngol Suppl 1998;539:71-5)
  • Erythromycin (Takizawa H, et al. J. Am J Respir Crit Care Med 1997;156:266-71)
  • Doxycycline (Attur MG, et al. J Immunol 1999 15;162:3160-7)
  • Minocycline (Attur MG, et al. J Immunol 1999 15;162:3160-7)

Other drugs that can suppress chemokines*:

  • ACE Inhibitors+ (Gullestad L, et al. J Am Coll Cardiol 1999;34:2061-7)
  • HMG-CoA reductase inhibitors # (Ortego M, et al. J. Atherosclerosis 1999;147:253-61)
  • Nitric oxide synthase inhibitors (Lane TE,et al. J Neurovirol 1999;5:48-54)
  • Ca(2+)-channel blockers (Rodler S, et al. J Mol Cell Cardiol 1995;27:2295-302)
  • PGE(2) including agents (Kunkel SL, et al. J Biol Chem 1988 15;263:5380-4)
  • Nucloside analogue (Zidek Z, et al. Eur J Pharmacol 1999 2;376:91-100)
  • Desferrioxamine (Martelius T, et al. Transplantation 1999 15;68:1753-61)
  • Pentoxifylline (Neuner P, et al. Immunology 1994 ;83:262-7)
  • Furosemide (Yuengsrigul A, et al. Ann Allergy Asthma Immunol 1999;83:559-66)
  • Thyroxine (Rittenhouse PA, and Redei E. Endocrinology 1997 ;138:1434-9)
  • Vitamin B3 (Pero RW, et al. Mol Cell Biochem 1999;193:119-25)
  • Vitamin B6 (Roubenoff R,et al. Arthritis Rheum 1995;38:105-9)
  • Vitamin B12 (Buccellato FR, et al. . FASEB J 1999;13:297-304)
  • Vitamin D (Harant H, et al.. Eur J Biochem 1997 15;250:63-71)
  • Progesterone (Vassiliadou N, et al. J Immunol 1999;15;162:7510-8)
  • Estrogens (Inadera H, et al. Endocrinology 2000;141:50-9)
  • Bile acids (Saitoh O, et al. J Gastroenterol Hepatol 1998;13:1212-7)
  • Ketamine (Kawasaki T, et al. Anesth Analg 1999;89:665-9)
  • Morphine (Grimm MC, et al. Ann N Y Acad Sci 1998 1;840:9-20)
  • Levodopa (Bessler H, et al. Biomed Pharmacother 1999;53:141-5)
  • Selegiline (Muller T, J Neural Transm Suppl 1998;52:321-8)
  • Sertraline (Maes M, et al. Neuropsychopharmacology 1999;20:370-9)
  • Trazadone (Maes M, et al. Neuropsychopharmacology 1999;20:370-9)
  • Haloperidol (Moots RJ, et al. Ann Rheumatic Dis 1999;58:585-7)

Chemokine and chemokine receptor blocking agents:

  • Heparin* (Ramdin L, et al. Clin Exp Allergy 1998;28:616-24)
  • Chondroitin (Kuschert GS et al. Biochemistry 1999;38:12959-68)
  • Mannans (Mbemba E, et al. Virology 1999;265:354-64)
  • Peptide (T Redwine LS, et al. Clin Immunol 1999;93:124-31)


-As shown above, a surprisingly large number of dietary supplements, herbal medicines, antibiotics and other commonly used drugs, have been shown to have an influence on chemokine production and activity. The list is incomplete and many more compounds may, on the appropriate testing, be shown to down regulate certain chemokines.

Useful information for the ultimate development of a standardized protocol to assist stealth virus infected patients should be forthcoming from serial determinations of levels of stealth virus infections on blood samples obtained prior to and following 2-4 week courses of various agents such as those included in the above table. For patients with minimal illnesses and especially in children, the initial emphasis should be on non-toxic dietary supplements and on over-the-counter medications. Thus it can be argued that maximum benefit from relatively non-toxic medications should precede the use of potentially toxic agents. If simple therapies fail, or if faced with more serious illnesses, it is appropriate to proceed with therapies that require professional medical dispensing and oversight. These drugs include a host of commonly prescribed anti-rheumatic medications, certain antibiotics and other drugs not widely known to influence chemokine levels and/or activity.

The clinical benefits seen with antibiotics have been ascribed to their ability to destroy pathogenic bacteria. The postulated targets for activity have included Borrelia (the cause of acute and classical Lyme disease), mycoplasma (a postulated cause of Gulf war syndrome and CFS). Chlamydia and rickettsiae (also presumed by some to be involved in the pathogenesis of CFS). As argued elsewhere, many of the assays supposedly supporting the presence of such bacteria, may actually reflect the assimilation of various bacterial sequences into stealth adapted viruses. The term "viteria" has been applied to stealth viruses that have acquired bacterial sequences. The pattern of clinical response to antibiotics is as consistent with an anti-chemokine action as with eradication of pathogenic bacteria. Furthermore, the use of antibiotics has the potential adverse effect of altering the body's bacterial flora. For this reason, it is probably preferable to try herbal and anti-rheumatic drugs before resorting to antibiotics. An exception to this argument is when specific testing identifies the presence of atypical bacteria or fungi that can be shown to be viteria infected.

The list does not include the use of accepted anti-viral agents, such as ganciclovir. Nor does it include therapies that are designed to address symptoms resulting from viral induced organ damage, especially damage that has occurred to the brain, endocrine organs, gastrointestinal tract, heart, blood, coagulation system, etc. Therapies for these and other manifestations of stealth viral illnesses need to be addressed on an individual basis.

Summary

While stealth virus research is still in the phase of discovery and characterization of individual isolates, it is important that efforts be underway to suppress the level of infection in those already infected. This may help minimize the risks of viral transmission and may also reduce the chances for emergence of more virulent, and even potentially oncogenic, stealth viruses. The present review has focused on agents that can influence cytokine/chemokine levels. This approach is bolstered by what is known about chemokines and chemokine receptors in conventional herpes viruses, data indicating expansions in the number of these genes in a prototype stealth adapted virus and by the knowledge base that many of these approaches have provided some relief to patients with diseases potentially due to stealth virus infections. Stealth virus monitoring of patients undergoing various therapies should help expedite the optimization of treatment protocals. Additional information and copies of published articles on stealth viruses are available from the web site www.ccid.org


© Copyright 2002 by W. John Martin, M.D., Ph.D., USA



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One Response to “Chemokines and Stealth Viruses:A Blueprint for Therapy in Infected Humans and Animals (Part II)”

  1. Chemokines and Stealth Viruses: A Blueprint for Therapy in Infected Humans and Animals (Part I) | Healing Base on December 9th, 2011 14:09

    […] Continued in Part II […]

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