Chapter 25 Immunomodulators Flashcards
What is the primary goal of immunostimulant therapy in equine patients?
To enhance endogenous immunity in a non-antigen-specific manner.
When might immunostimulant therapy be used prophylactically in horses?
Prior to pathogen challenge or stressful situations like weaning or long-distance transport.
In what settings is immunostimulant therapy used concurrently with antimicrobial therapy?
To further enhance endogenous immune clearance mechanisms in combination with targeted pathogen treatment.
What are some immunologic mechanisms involved in innate immunity?
Rapid destruction of invading pathogens without memory or antigenic specificity, and activation of adaptive responses via antigen-presenting cells.
What is the role of pattern recognition receptors (PRRs) in innate immunity?
They recognize pathogen-associated molecular patterns (PAMPs) and initiate immune responses.
What are some examples of pattern recognition receptors (PRRs)?
Mannose receptor, CD14, peptidoglycan recognition protein (PGRP), scavenger receptors (SR), Toll-like receptors (TLRs), and nucleotide oligomerization domain/caspase recruitment domain (NOD/CARD).
What is the significance of Toll-like receptors (TLRs) in innate immunity?
They recognize microbial, viral, and fungal conserved structures and play a crucial role in immune response activation.
What is the function of Toll-like receptor-9 (TLR-9)?
Recognizes unmethylated CpG-containing DNA motifs found in intracellular bacteria and viruses.
What is the role of Toll-like receptor-7 (TLR-7)?
Recognizes small synthetic immune modifiers and has applications in clinical use against viral infections and cancers.
What are some commercially available immunostimulants for use in horses?
Inactivated Parapoxvirus ovis (Zylexis), Propionibacterium acnes extract (EqStim), Mycobacterial cell wall extract (Equimune IV), Interferon-alpha (Intron A), Imiquimod (Aldara), Granulocyte-colony stimulating factor (Neupogen), and Levamisole phosphate.
What is Inactivated Parapoxvirus ovis (iPPVO) used for in horses?
To enhance immunity before a stressful event or during disease, particularly for respiratory disorders caused by equine herpesvirus-1 (EHV-1) and EHV-4.
What are the immunologic benefits of Inactivated Parapoxvirus ovis (iPPVO)?
Activation of antigen-presenting cells (APCs) and up-regulation of inflammatory cytokines IL-6, IL-8, TNF-alpha, and Th1 response-inducing cytokines IL-12 and IL-18.
What is the role of Propionibacterium acnes extract (EqStim) in equine medicine?
Treatment of chronic, exudative respiratory disease and prophylactic administration prior to stressful events that may impair pulmonary defense mechanisms.
What are the effects of Propionibacterium acnes on the immune system?
Stimulation of macrophage function, natural killer cytotoxicity, cytokine production (IL-1, IFN-gamma), and enhanced immune activation.
What is Mycobacterial cell wall extract (MCWE) used for in horses?
Treatment of infectious respiratory disease and post-breeding endometritis.
What is the mechanism of action of Mycobacterial cell wall extract (MCWE)?
Potent stimulation of nonspecific immunity, inducing cytokine production and enhancing immune responses.
What is the role of Interferon-alpha (IFN-alpha) in equine immunomodulation?
Demonstrates antiviral, immunomodulatory, and antiproliferative properties, and enhances natural killer cell cytotoxicity and macrophage activation.
What are the benefits of oral administration of IFN-alpha in horses?
Reduces inflammation in the lower respiratory tract, lowers total cell counts in bronchoalveolar lavage fluid (BALF), and converts the differential cell count to a non-inflammatory cytologic profile.
What is the therapeutic use of Imiquimod in horses?
Treatment of aural plaques, sarcoid skin tumors, and sweat gland ductal carcinoma.
What is the mechanism of action of Imiquimod?
A TLR-7 ligand that stimulates dendritic cells to secrete pro-inflammatory cytokines for T cell activation.
What is Granulocyte-colony stimulating factor (G-CSF) used for in horses?
Treatment and prophylaxis of neutropenia resulting from sepsis, endotoxemia, and drug-induced myeloid hypoplasia.
What is the effect of Granulocyte-colony stimulating factor (G-CSF) on neutrophils?
Increases the number of precursor cells, enhances neutrophil production, and shortens the maturation time.
What is Levamisole phosphate used for in horses?
It has been suggested as an adjunct treatment for equine protozoal myelitis (EPM) and may have immune-stimulating capabilities.
What is the potential benefit of Levamisole phosphate in immune-stimulating therapy?
Enhances lymphoproliferative responses and cell-mediated immune responses, potentially useful in stress, aging, or immune system immaturity.
What are the common clinical applications of Inactivated Parapoxvirus ovis (iPPVO) in horses?
Enhancement of immunity before stressful events and during respiratory disease episodes.
What is the recommended dosing protocol for Inactivated Parapoxvirus ovis (iPPVO)?
2 mL intramuscular injection on days 0, 2, and 9, or a similar three-dose series during disease episodes.
What are the observed effects of Inactivated Parapoxvirus ovis (iPPVO) on cytokine expression?
Increased peripheral blood mononuclear cell (PBMC) cytokine expression and enhanced phagocytosis and oxidative burst activity of neutrophils.
What is the role of Propionibacterium acnes extract (EqStim) in enhancing immune function?
Increases distribution of T helper and cytotoxic lymphocyte populations, and enhances non-opsonized phagocytic activity and cytokine expression.
What are the dosing recommendations for Propionibacterium acnes extract (EqStim)?
Intravenous dose of 1 mL/113 kg (or 250 lbs) on days 1, 3 (or 4), and 7.
What are the potential side effects of Mycobacterial cell wall extract (MCWE) in horses?
Pulmonary lesions, including multifocal granulomatous pneumonitis and bronchiolitis, particularly after multiple intravenous administrations.
What is the therapeutic effect of Interferon-alpha (IFN-alpha) in horses with inflammatory airway disease (IAD)?
Reduces exudate in the respiratory tract, lowers total cell counts in bronchoalveolar lavage fluid (BALF), and converts the differential cell count to a non-inflammatory cytologic profile.
What is the effect of Imiquimod on virus-associated skin lesions in horses?
Shows favorable results in treating aural plaques, sarcoid skin tumors, and sweat gland ductal carcinoma.
What is the recommended treatment protocol for Imiquimod in horses?
Application of a thin layer of 5% cream to lesions three times a week, every other week, for a minimum of 16 weeks.
What are the benefits of Granulocyte-colony stimulating factor (G-CSF) in postoperative horses?
Enhances immunity by promoting the number and function of circulating neutrophils, aiding recovery after surgery.
What is the mechanism of action of Levamisole phosphate in immune modulation?
Enhances lymphoproliferative responses and cell-mediated immune responses, potentially useful in stress, aging, or immune system immaturity.
What are the clinical indications for the use of immunostimulants in horses?
Enhancement of immune function before stressful events, during disease episodes, and in combination with antimicrobial therapy.
What is the effect of Propionibacterium acnes on pulmonary lymphocytes in horses?
Reduced lymphocyte counts in bronchoalveolar lavage fluid (BALF), possibly due to margination into regional lymphoid tissues or resolution of sub-clinical pulmonary infection.
What is the significance of cytokine expression following immunostimulant therapy?
Indicates an immune response shift that may provide an immunologic advantage through anti-viral and cytokine-inducing mechanisms.
What are the potential benefits of using Mycobacterial cell wall extract (MCWE) in mares with endometritis?
Reduction in uterine inflammation and increased pregnancy rates when combined with standard care therapy.
What is the role of Interferon-alpha (IFN-alpha) in reducing respiratory tract inflammation?
Stimulates Th1 cellular activation, enhancing natural killer cell cytotoxicity, macrophage activation, and cytokine production.
What are the observed effects of Imiquimod treatment on aural plaques in horses?
Complete resolution of plaques in horses, with a treatment protocol involving application of 5% cream three times a week for several months.
What is the clinical outcome of Granulocyte-colony stimulating factor (G-CSF) administration in neonatal foals?
Increases neutrophil counts and may provide prophylactic protection against neonatal infections.
What are the immunomodulatory effects of Propionibacterium acnes extract (EqStim) in foals?
Enhanced PBMC IFN-gamma and host defense peptide expression, and increased bactericidal activity in leukocytes.
What is the impact of Inactivated Parapoxvirus ovis (iPPVO) on foal neutrophil function?
Increased phagocytosis and oxidative burst activity, suggesting potential benefits in enhancing immune responses.
What is the potential therapeutic use of Levamisole phosphate in equine protozoal myelitis (EPM)?
Adjunct treatment at 1 mg/kg PO SID, with potential synergistic effects with other antiparasitic drugs.
What are the observed benefits of using Propionibacterium acnes extract (EqStim) in horses during long-distance transport?
Reduced incidence of respiratory disease and improved clinical outcomes compared to control groups.
