Immunotherapy in Veterinary Medicine

Immunotherapy: An Overview

Immunotherapy, also known as biological therapy, is a treatment approach that modulates the immune system, either by activating or suppressing it, to combat disease. Understanding the different types of immunotherapies is crucial for modern veterinary medicine.

Activation vs. Suppression Immunotherapies

Activation Immunotherapies: Designed to elicit or amplify an immune response, enhancing the body's natural defenses.
Suppression Immunotherapies: Focus on reducing or suppressing the immune response, crucial when the immune system is overactive.

The distinction between these types is essential for tailoring immunotherapy to individual animal needs. While primarily recognized in human medicine, immunotherapy is increasingly applied in veterinary medicine, especially for immune-mediated diseases in dogs, cats, and horses.

Immunosuppressive Agents

Glucocorticoids

Serve as both anti-inflammatory and immunosuppressive drugs, affecting both innate and adaptive immune responses.
Mechanism:
- Bind to cytoplasmic glucocorticoid receptors (GCGR).
- The GCGR complex translocates to the cell nucleus.
- Stimulates or inhibits gene transcription, reducing inflammation and relieving pain.
Common Uses: Treat allergic skin diseases and feline asthma.
Side Effects: Can lead to blanket immunosuppression.
Mimic the effects of endogenous corticosteroids.

Cytotoxic Drugs

Target the cell cycle and are commonly used in treating autoimmune diseases in dogs.
Cell Cycle Phases:
- M phase: Mitosis occurs.
- G1 phase: RNA and protein synthesis.
- G0 phase: Resting state.
- S phase: DNA, RNA, and protein synthesis.
Examples: Azathioprine and cyclophosphamide, often used in addition to glucocorticoids for additive immunosuppressive effects.
Benefit: Can provide steroid-sparing effects, which is beneficial in managing disease.

Cyclosporine

An anti-T cell medication originally developed for transplantation.
Applications: Treating allergies and inflammatory diseases in dogs.
Side Effects:
- Increased risk of infection.
- Diarrhea or shedding.
- Potential liver and kidney damage.

Janus Kinase (JAK) Inhibitors

Block the JAK-STAT signaling pathway.
Mechanism:
- Cytokines bind to cytokine receptors, activating JAK kinases.
- JAK kinases phosphorylate transcription factors, leading to cytokine production.
- JAK inhibitors inhibit STAT phosphorylation, downregulating inflammatory cytokine production.
Application: Treatment of canine allergic dermatitis.

Immunostimulatory Agents

Enhance the immune response; however, there are few licensed drugs available in this category.

Plant or Microbial Extracts

Lethamenosol: Once used but no longer recommended for dogs due to safety concerns.
Microbial Extracts: Drive a strong Th1 immune response, important for fighting certain infections.
Parapox Ovis: Associated with equine stress-related respiratory disease.

Allergen-Specific Immunotherapy (Hyposensitization)

Involves repeated injections of causative allergens.
Aims to generate blocking antibodies and activate regulatory T cells (Tregs).
Beneficial in treating canine atopic dermatitis.

Intravenous Immunoglobulin Therapy

Uses purified human immunoglobulins.
Mechanism:
- Binds to macrophage Fc receptors, modulating immune responses.
- Blocks the interaction between Fas and Fas ligand, regulating cell death.
Useful for conditions like canine immune-mediated hemolytic anemia, thrombocytopenia, and autoimmune skin diseases.
Cytokine therapy

-Involves the use of Cytokines to modulate the immune response.
-Example: Treatment of neutropenia in dogs. Recombinant human cytokine GCSF is injected into dogs which stimulates bone marrow production to produce more white blood cells.
-Antibodies raised against the human version can also block the function of the dog GSV by cross reaction so it's a balancing act for treatment.
-Cytokine therapy can include the use of genetic material to enhance the production of cytokines i.e messenger RNA to deliver a particular cytokine or a bacterial plasmid such as DNA to produce that as a vector for producing a particular cytokine.

Monoclonal Antibody Therapy

Specifically blocks various aspects of the immune response, including:

Inhibiting antigen presentation.
TCR T cell activation.
Cytokine binding.
Lymphocyte homing.

Development of Monoclonal Therapy

An antibody used against the cytokine used for blocking pain in humans (unsuccessful) turned into a canine antibody and used for the treatment of pain in dogs. The research is being implemented into cats and horses as well.

Parasite Therapy

Based on the hygiene hypothesis, which suggests that exposure to germs and infections during childhood is beneficial for the immune system's development. This helps the immune system respond appropriately and not overreact to harmless substances.

Pig Whipworm Model

Used in humans to treat autoimmune diseases like irritable bowel syndrome.
Mechanism:
- Pig whipworm eggs are ingested and hatch within the human body.
- The worms modulate the immune response in the stomach.
- Changes the microbiome due to decreased bacterial attachment and in bacterial diversity. This process promotes a type two Tregs response.
- Direct secretion of anti-inflammatory molecules and promotion of barrier function by increased mucus production of globulin cells.
Potential for treating autoimmune diseases in cats and dogs.

Gene Therapy

A promising approach for treating monogenetic genetic disorders caused by a single gene mutation. It aims to correct the underlying genetic defect and induce tolerance to specific proteins.

Being adopted into veterinary medicine for dogs and horses.

Adjunct Immunotherapy

Gaining attention and includes complementary treatments:

Acupuncture.
Herbal medicines.
Plant extracts and dietary supplements.
CBD from cannabis: Used to treat separation anxiety in pets.