Page 334 - Clinical Small Animal Internal Medicine

302 Section 4 Respiratory Disease

with ciclosporin use in cats include anorexia and gastro- of IgE‐blocking antibodies, induction of T cell
VetBooks.ir intestinal upset. Nephrotoxicity and hepatotoxicity may unres ponsiveness, shift from a T helper 2 to a T helper
1 cell response, elaboration of immunosuppressive
develop at high blood levels.
Antiserotonergics, antileukotrienes, and antihista-
decreased lymphocyte proliferation in response to aller-
mines have been investigated for use in feline asthma to cytokines such as IL‐10 from T regulatory cells, and
reduce airway inflammation while circumventing the gen. In cats experimentally sensitized to Bermuda grass
adverse effects associated with systemic glucocorticoid allergen (BGA), RIT significantly decreased eosinophilic
therapy. Serotonin released during mast cell degranula- airways inflammation, induced lymphocyte hyporespon-
tion mediates airway smooth muscle contraction in cats. siveness to BGA, increased mRNA transcription of IL‐10
Cyproheptadine, a serotonin receptor antagonist, has in BAL fluid, and decreased mRNA transcription of IL‐5
been shown to attenuate constriction of airway smooth in BAL fluid. Adverse effects associated with RIT in this
muscle from antigen‐sensitized cats in vitro. In live cats model included localized swelling around the injection
experimentally sensitized to aeroallergen, cyprohepta- site, increased heart and respiratory rate, hyperthermia,
dine did not uniformly diminish airway responsiveness, vomiting, agitation, and systemic anaphylaxis noted in
degree of airway eosinophilic inflammation, plasma or one cat. These adverse effects were less severe when RIT
BAL fluid serotonin concentrations, or serum content of was adjuvanted with CpG oligodeoxynucleotides, immu-
allergen‐specific IgE following allergen challenge. nostimulatory DNA sequences that induce a polarized
Similarly, cysteinyl leukotrienes are produced by mast Th1 response. Intranasal administration of RIT has also
cells as well as eosinophils and contribute to many of the been evaluated in an experimental model of feline
pathophysiologic processes underlying asthma, includ- asthma and was shown to be equally effective in reduc-
ing bronchoconstriction, smooth muscle proliferation, ing the degree of eosinophilic airway inflammation as
mucus production, and inflammatory cell influx. The subcutaneously administered RIT, although subcutane-
leukotriene receptor antagonist zafirlukast was evalu- ous RIT more consistently abolished the clinical signs
ated in an experimental model of feline asthma and was induced by aeroallergen challenge. Both antiinflamma-
demonstrated to have no effect on airway eosinophilia, tory and immunomodulatory therapy may be necessary
airway reactivity, or serum levels of allergen‐specific IgE in severely affected cats. When administered concur-
compared to placebo. In another study, urine concentra- rently with RIT, oral glucocorticoid therapy has been
tions of cysteinyl leukotrienes in allergen‐sensitized cats shown to dampen the long‐term effectiveness of RIT,
did not increase after allergen challenge. These results which may limit the benefits of RIT as monotherapy in
suggest that leukotrienes may not be a critical factor patients with severe disease.
in the generation of the feline asthmatic response. The challenge in applying RIT to cats with naturally
Histamine plays a crucial role in inducing bronchocon- occurring asthma lies in elucidating which antigen is
striction in human asthmatics, though its importance in triggering the asthmatic response. Intradermal skin test-
mediating the feline asthmatic response remains ques- ing has been employed to identify the inciting antigens in
tionable. Cetirizine is a second‐generation histamine 1 veterinary patients with atopic dermatitis. This method
receptor antagonist that has been evaluated in cats with has been shown to be highly sensitive in detecting a
experimentally induced asthma and was shown to have known inciting antigen in cats artificially sensitized to a
no effect on eosinophilic airway inflammation or plasma specific allergen. Concurrently, detection of allergen‐
histamine concentrations. Until additional studies are specific IgE in the serum of experimentally sensitized
conducted, pharmaceutical agents that inhibit serotonin, cats was shown to be highly specific in identifying the
leukotrienes, and histamine are not recommended as antigen used for sensitization. When evaluated in cats
monotherapy in the management of feline asthma. with naturally occurring small airway disease, signifi-
Allergen‐specific immunotherapy holds promise as cantly more positive allergen reactions on serum IgE
the only potentially curative therapy for feline asthma. testing and intradermal skin testing were noted com-
This form of therapy, which is most commonly employed pared to cats without airways disease, though the clinical
in veterinary medicine in the management of atopic der- relevance of these allergens could not be determined.
matitis, is proposed to alter the immune response so as Even though isolating the specific inciting antigen is the
to reestablish tolerance to a specific allergen. In particu- ideal means of guiding immunotherapy, RIT using anti-
lar, rush immunotherapy (RIT) is a modified version of gens that did not completely match those used to induce
allergen‐specific immunotherapy that involves subcuta- the asthmatic phenotype in experimental feline models
neous administration of gradually increasing doses of a was shown to reduce eosinophilic airways inflammation.
specific antigen over an accelerated period of time, gen- Immunotherapy is likely to play a prominent role in the
erally a couple of days or less. The immunomodulatory management of feline asthma in the future, but addi-
effects of RIT are hypothesized to be related to production tional studies in patients with naturally occurring disease