Screening of Immunomodulatory Drugs

Definition, rationale & the immune targets assays probe

• Definition — Immunomodulator screening is the preclinical bench-and-animal battery that detects whether a test compound suppresses (immunosuppressant) or augments/restores (immunostimulant) an immune response, and grades its potency against reference standards.
• The immune response is functionally partitioned; each arm has its own validated read-out, and a screening cascade typically samples ≥ 3 arms to profile a compound:
  • Humoral (antibody-mediated) — B-cell/plasma-cell output → plaque-forming-cell (PFC) assay to SRBC; haemagglutination antibody titre.
  • Cell-mediated immunity (CMI) — T-cell effector function → delayed-type-hypersensitivity (DTH) footpad swelling; mitogen-/MLR-driven lymphocyte proliferation; leucocyte-migration-inhibition.
  • Non-specific / innate & reticuloendothelial (RES) — macrophage/neutrophil oxidative burst & phagocytosis → chemiluminescence, carbon-clearance phagocytic index, neutrophil-adhesion.
  • Effector hypersensitivity — mast-cell/IgE-mediated reactions (anaphylaxis, Arthus) as models of drug-modifiable allergic inflammation.
• Why both tiers — In-vitro assays (enzyme, cell-culture proliferation) allow high-throughput lead selection with tiny compound amounts; whole-animal models test the compound in an intact, cytokine-networked immune system that no single cell assay reproduces.
• Translation caveat — Mouse models of inflammatory/immune disease correlate poorly with human disease; the trend is toward rat models for superior pain behaviour and surgical tractability.