Table 3.
Medications that Target the Immune Response.
| Targets | Class | Drugs | Mechanism | Indications |
|---|---|---|---|---|
| Nitric oxide, NF-kB, proteasome, cytokines | HMG-CoA reductase inhibitors (statins) | Simvastatin, Atorvastatin, Cerivastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin | Inhibits RLS in cholesterol synthesis and decreases circulating lipids while also decreasing C-reactive protein levels and reducing inflammation | Cardiovascular; Hepatic; Metabolic *NCT04348695 *NCT04380402 |
| NF-κB pathway | Anti-TNF agents | Adalimumab, Certolizumab pegol, Etanercept, Golumumab, Infliximab | Inhibits TNF cell signals | Rheumatic *NCT04425538 |
| NF-κB pathway | Protease antagonists | Bortezomib, Carfilzomib, Ixazomib | Inhibits proteasomes responsible for cell homeostasis and promotes proapoptotic activity | Cancer |
| NF-κB pathway | Interleukins | Rilonacept (IL-1) Anakinra (IL-1R) Canakinumab (IL-1β) Tocilizumab (IL-6R) Sarilumab (IL-6R) Siltuximab (IL-6) Brodalumab (IL-17) Ixekizumab (IL-17) Secukinumab (IL-17) |
Cytokines involved in immunoregulatory and inflammatory processes | Cancer *NCT04443881 *NCT04362813 *NCT04377659 *NCT04315298 *NCT04329650 *NCT04403243 |
| Pattern-recognition receptors, toll-like receptor 3 | Interferons |
Interferon Alfa-2b, Interferon Alfa-n3, Interferon Beta-1a, Interferon Gamma-1b, PEG interferon Alfa- 2a, PEG interferon Alfa-2b, PEG interferon Beta-1a |
Cytokines which have antiviral response activity and immunomodulatory capacity | CNS; Cancer *NCT04379518 *NCT04449380 |
| Stress | Systemic glucocorticoids | Betamethasone, Budesonide, Cortisone, Cosyntropin (ACTH), Deflazacort, Dexamethasone, Fludrocortisone, Hydrocortisone, Methylprednisolone, Prednisolone, Prednisone, Triamcinolone | Anti-inflammatory actions include suppression of neutrophil function and inhibition of prostaglandin synthesis | Allergy; Autoimmune; Dermatologic; Respiratory; Cancer; Gastrointestinal; Hematologic; Ophthalmic; Rheumatic; Renal *NCT04361474 *NCT04325061 *NCT04359511 *NCT04263402 *NCT04344288 |
| Cytokines/Mast Cell | Antihistamines 1st generation 2nd generation |
Diphenhydramine, Pyrilamine, Doxylamine, Brompheniramine, Dexbrompheniramine, Carbinoxamine, Chlorpeniramine, Clemastine, Dexchlorpheniramine, Dimenhydrinate, Meclizine, Promethazine, Triprolidine Acrivastine, Certizine, Desloratidine, Fexofenadine, Levocertirizine, Loratadine |
Competitive for H1 receptors on effector cells (gastrointestinal, respiratory, blood vessels); sedating Competitive for H1 receptors on effector cells (gastrointestinal, respiratory, blood vessels); does not cross BBB, less sedating |
Allergic Reactions |
| Cytokines/Mast Cell | Histamine 2 antagonists | Famotidine, Cimetidine, Nizantidine, Ranitidine | Competitively inhibits the histamine H2 receptor on the parietal cells to decrease gastric acid secretion | Mast cell disease, Gastro-esophageal reflux *NCT04370262 |
| Cytokines/Mast Cell | Leukotriene receptor antagonists | Montelukast, Zarfilukast | Selective antagonist of cysteinyl leukotrienes to reduce airway inflammation and edema | Asthma *NCT04389411 |
| Cytokines/Mast Cell | Mast cell stabilizers | Cromolyn, Ketotifen | Inhibits the release of histamine, leukotrienes, and mediators | Systemic mastocytosis; Asthma |
| JAKs | Janus Associated Kinase | Baricitinib, Fedratinib, Ruxolitinib, Tofacitinib, Upadacitinib | Inhibits JAK-induced cytokine and growth factor expression and signaling activity, including STAT activation | Rheumatoid Arthritis *NCT04421027 *NCT04377620 *NCT04412252 |
| Substance P | Neurokinin-1 receptor antagonist | Aprepitant, Fosaprepitant, Netupitant, Rolapitant | Selectively and competitively inhibits substance P binding to neruokinin-1 and downstream signals | Antiemetic |
| COX-2 | Cyclooxygenase (COX)-II Selective | Celecoxib, Parecoxib, Etoricoxib | Selective inhibition of COX-2 decreases prostaglandin synthesis; anti-inflammatory; antipyretic; analgesic | Pain; Arthritis |
Shown are medications that suppress adaptive and innate immune responses.
CNS, central nervous system; HMG-CoA reductase, 3-hydroxy-3-methylglutaryl coenzyme A reductase; RLS, rate limiting step; PEG, polyethylene glycol; NFκB, nuclear factor kappa B; TNF, tumor necrosis factor. Infix -zu denotes a humanized monoclonal antibody. Suffix –mab indicates a monoclonal antibody. Suffix -ib denotes a small molecule inhibitor. *Select ClinicalTrials.gov Identifier for the testing of the highlighted listed class of drugs in COVID-19.