ubiquinone and Immunologic-Deficiency-Syndromes

The isoprenoid pathway produces three key metabolites--digoxin (membrane Na+-K+ ATPase inhibitor, regulator of neurotransmitter transport, and an immunomodulatory agent), dolichol (a regulator of N-glycosylation of proteins), and ubiquinone (a free radical scavenger). The pathway was assessed in acute rheumatic fever patients with recurrent streptococcal infections, and who were also studied for differences in right and left hemispheric dominance. The isoprenoid pathway was downregulated with decreased digoxin synthesis in these patients and in those with left hemispheric chemical dominance. The tryptophan catabolites were decreased and the tyrosine catabolites increased. In these groups of patients the dolichol and glycoconjugate levels were reduced and lysosomal stability was increased. The ubiquinone levels were elevated and free radical levels decreased in these patients. The membrane cholesterol:phospholipid ratios were decreased and membrane glycoconjugates increased. On the other hand in right hemispheric chemical dominance the reverse patterns and hyperdigoxinemia with an upregulated isoprenoid pathway were noticed. The role of the isoprenoid pathway in the pathogenesis of acute rheumatic fever and recurrent streptococcal infections and its relation to hemispheric chemical dominance is discussed.

Topics: Acute Disease; Adolescent; Analysis of Variance; Child; Digoxin; Disease Susceptibility; Dolichols; Dominance, Cerebral; Down-Regulation; Enzyme Inhibitors; Erythrocyte Membrane; Glycoproteins; Glycosaminoglycans; Humans; Hydroxymethylglutaryl CoA Reductases; Immunologic Deficiency Syndromes; Magnesium; Matched-Pair Analysis; Neuroimmunomodulation; Neurotransmitter Agents; Pharyngitis; Polyisoprenyl Phosphates; Recurrence; Rheumatic Fever; Sodium-Potassium-Exchanging ATPase; Streptococcal Infections; Ubiquinone

Three classes of immunostimulating drugs are described, each representing a different approach to the problem of pharmacological immunostimulation. The rationale for the use of microbes or microbial agents as immunostimulators rests on the fact that some micro-organisms, especially those that replicate intracellularly, carry a special potential to activate macrophages. Clinically, the use of these agents in patients with tumors and infections has been disappointing; however, there have been positive exceptions like the responsiveness of melanomas and bladder carcinomas to the injection of BCG. Many of the inconclusive results may be due to insecurities in the dosage of microbial preparations and to a general lack in standardization. Some structures with high efficacy and low toxicity which have recently evolved from this field deserve further investigation. A number of structurally unrelated synthetic compounds was found to influence immune parameters. Levamisole can today be classified as an immunostimulating drug with limited utility in recurring infections and in chronic polyarthritis. Several immunostimulating drugs which have attracted interest contain a purine as the effective component. This is not surprising in view of the fact that many genetically determined immunodeficiencies can be traced to defects of enzymes which play a crucial role in purine biosynthesis. Finally, the potential role of lymphokines as stimulators of the immunosystem is briefly described. Some of these glycoproteins have recently become available for clinical trials. Others will be made available through genetic engineering. The therapeutic utility of these compounds is not yet clear; they will, however, be of great value as probes for the study of immune functions and for the development of immunopharmacology.

Topics: Adjuvants, Immunologic; Animals; Bacterial Infections; Bacterial Vaccines; Humans; Immunity, Cellular; Immunization; Immunologic Deficiency Syndromes; Mice; Neoplasms; Polysaccharides, Bacterial; Ubiquinone