Antibiotics

• Macrolides (e.g., Azithromycin, Erythromycin)

  • Mechanism: Significant anti-inflammatory and immunomodulatory effects by inhibiting pro-inflammatory cytokines (e.g., IL-8) and reducing neutrophil migration and activity. Erythromycin also acts as a motilin receptor agonist.
  • Non-Infectious Uses:
    • Chronic Respiratory Diseases: Used in conditions like COPD, bronchiectasis, and diffuse panbronchiolitis to reduce exacerbations and inflammation.
    • Gastroparesis: Erythromycin is used for its prokinetic effect on the GI tract.
    • Severe Asthma: May be used as an add-on therapy in certain phenotypes.

• Tetracyclines (e.g., Doxycycline, Minocycline)

  • Mechanism: Exert anti-inflammatory effects by inhibiting matrix metalloproteinases (MMPs), which are involved in tissue degradation and inflammation. They also suppress angiogenesis and apoptosis.
  • Non-Infectious Uses:
    • Dermatology: Acne vulgaris and rosacea (at sub-antimicrobial doses), bullous dermatoses, and pyoderma gangrenosum.
    • Rheumatology: Used as a disease-modifying agent in rheumatoid arthritis (RA) and scleroderma.
    • Ophthalmology: Treatment of posterior blepharitis and meibomian gland dysfunction.

• Sulfones (e.g., Dapsone)

  • Mechanism: Primarily anti-inflammatory, thought to work by inhibiting neutrophil chemotaxis and function via myeloperoxidase inhibition.
  • Non-Infectious Uses:
    • Dermatology: First-line treatment for dermatitis herpetiformis; also used for other neutrophilic dermatoses like linear IgA bullous dermatosis and pemphigus.

Antifungals

While most are used for infections, some with macrolide structures are cornerstones of immunosuppression.

• Calcineurin Inhibitors (e.g., Tacrolimus)

  • Mechanism: This macrolide-like drug is a potent immunosuppressant that inhibits calcineurin, thereby blocking T-cell activation and cytokine production.
  • Non-Infectious Uses:
    • Transplant Medicine: Mainstay therapy to prevent solid organ transplant rejection.
    • Dermatology: Used topically (Tacrolimus, Pimecrolimus) for atopic dermatitis and other inflammatory skin conditions.

• mTOR Inhibitors (e.g., Sirolimus [Rapamycin])

  • Mechanism: This macrolide-like drug inhibits the mammalian Target of Rapamycin (mTOR), a key kinase in cell proliferation, leading to immunosuppressive and anti-proliferative effects.
  • Non-Infectious Uses:
    • Transplant Medicine: Used to prevent organ rejection, often in patients who cannot tolerate calcineurin inhibitors.
    • Cardiology: Coated on coronary stents to prevent restenosis.
    • Oncology: Treatment for certain cancers (e.g., perivascular epithelioid cell tumors).

• Azoles (e.g., Ketoconazole)

  • Mechanism: Inhibits fungal cytochrome P450 enzymes but can also inhibit human steroidogenesis at higher doses.
  • Non-Infectious Uses:
    • Endocrinology: Used as a second- or third-line agent to lower cortisol levels in Cushing's syndrome.

Antivirals

The use of antiviral drugs for primary non-infectious diseases is not common or well-established. Their clinical application is almost exclusively for treating viral infections.

• Immunomodulatory Effects: While some antivirals like remdesivir have been noted to have immunomodulatory effects (e.g., downregulating pro-inflammatory cytokines), this is typically studied within the context of treating a viral infection (e.g., COVID-19) and not as a primary therapy for a non-viral inflammatory disease. Research into the broader immunomodulatory potential of antivirals is ongoing.