Mediated Immunomodulation

Cop-1 Reactive Cells Memory T Cells Regulatory T Cells 

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Plants and microorganisms produce unique and diverse chemical stmctures, some of which act as immunomodulators (18—28). Of specimens used in traditional medicine, approximately 450 plant species have shown antiviral activity out of 4000 plants screened (19). Several tannins (20) exhibit strong inhibition of tumor promotion experimentally. Pretreatment of mice with small amounts of tannins for several days strongly rejected transplanted tumors. This activity has been claimed to be effected through enhancement of host-mediated antitumor activity. 

P10. Philip, R., and Epstein, L. B., Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature 323, 86-89(1986). 

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

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.

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

SSRIs-FLUOXETINE IMMUNOMODULATING DRUGS-CICLOSPORIN t plasma concentrations of cidosporin with risk of nephrotoxicity, myelosuppression and neurotoxicity Inhibition of CYP3A4-mediated metabolism of cidosporin these inhibitors vary in potency Monitor plasma cidosporin levels to prevent toxicity... 

APREPITANT ANTICANCER AND IMMUNOMODULATING DRUGS-CORTICOSTEROIDS t dexamethasone and methylprednisolone levels Inhibition of CYP3A4-mediated metabolism of these corticosteroids Be aware... 

TOPIRAMATE ANTICANCER AND IMMUNOMODULATING DRUGS-IMATINIB t topiramate levels Imatinib is a potent inhibitor of CYP2C9-mediated metabolism of topiramate Watch for the early features of toxicity. If necessary, consider using alternative drugs while the patient is being given imatinib... 

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