Animals Immunostimulants

In contrast to adjuvants, immunostimulants do not need to be administered together with antigen to enhance immunity. They are generally given to induce a short-term, nonantigen-specific enhancement of the immune system. They appear to be most useful when treating chronic diseases in which there is good evidence of immunosuppression. They are used in the therapy of equine sarcoid, bovine papilloma, equine respiratory disease, equine endometritis, chronic skin diseases (eg, staphylococcal pyoderma or demodicosis), certain tumors of dogs and cats, and immunosuppressive viral diseases (eg, feline leukemia).

Many bacteria have been utilized as immunostimulants. The most potent of these is BCG, the live attenuated vaccine strain of Mycobacterium bovis . BCG produces a generalized enhancement of both B- and T-cell-mediated responses and of phagocytosis, graft rejection, and resistance to infection. Because BCG causes tuberculin sensitivity, these organisms must be fractionated to remove the reactive material. Thus, mycobacterial cell wall fractions, muramyl dipeptide (MDP), and trehalose dimycolate have all been used as immunostimulants. MDP, the most potent factor from mycobacteria, enhances antibody production and stimulates and activates macrophages.

Another organism, Propionibacterium acnes also promotes a generalized enhancement of nonspecific immunity. The cell wall of P acnes contains MDP and lipid compounds that are immunostimulatory. This material has a complex activity because it stimulates phagocytosis by macrophages and neutrophils; increased activity of natural killer cells; development of T and B lymphocytes; and increased production of interleukin-1, interferons, and tumor necrosis factor. Pacnes also increases resistance to infection by many pathogenic bacteria and viruses. It is administered into the circulatory system and is used in therapy of dogs with pyoderma, cattle with bovine papilloma, and horses with respiratory disease and chronic endometritis. Clinical reports indicate some success in the treatment of symptomatic feline leukemia and as an adjunct to surgery in the treatment of oral melanoma in dogs.

Cell wall components of Staphylococcus aureus administered SC in dogs stimulate the production of interleukin-1, interleukin-6, tumor necrosis factor, and γ interferon. This product is used successfully in the treatment and management of Staphylococcus -associated pyoderma in dogs. Dogs occasionally become sensitized to this material.

Acemannan is a long-chained mannan extracted from Aloe vera (barbadensis) . It stimulates macrophages, induces cytokine production, and enhances cellular immunity. It is indicated for wound healing, as adjunct therapy for fibrosarcoma of dogs and cats, and in the management of feline retroviral diseases.

Endotoxins from gram-negative bacteria enhance antibody formation if given at about the same time as the antigen. They have a general immunostimulatory activity because they act through toll-like receptors to induce innate resistance to bacterial infections.

Certain complex carbohydrates, eg, zymosan, glucan, dextran sulfate, and lentinans, are immunostimulants and can activate macrophages.