Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 12 IMMUNOMODULATORY THERAPY
receive a range of therapeutics (e.g. antibiotics, fluids,
vitamins, nonsteroidal anti-inflammatory drugs) which
should be used cautiously after appropriate risk : benefit
analysis.
Special considerations
Special care should be taken by those administering this
product. If accidentally self-injected, medical assistance
should be sought immediately.
Interleukin-2
Recombinant human interleukin-2 (rHuIL-2) has been
administered as adjunct therapy (with surgical resection
and/or chemotherapy) to dogs with neoplastic disease
in order to enhance the endogenous antitumor immune
response. Patients with a range of tumors have been
studied, but greatest promise came from sequential
administration of rHuTNF and rHuIL-2 to dogs with
oral melanoma or mast cell tumors. rHuIL-2 has been
administered by IV or SC injection, or by nebulization
of IL-2 or liposomes containing IL-2 in an attempt to
reduce the formation of pulmonary metastases.
Recent studies have shown that injected cDNA encoding
the IL-2 sequence localizes to the lung and transfects
pulmonary cells that subsequently produce IL-2. rHuIL-
2 has been coadministered with rHuIFN-α to cats with
FeLV-induced disease, but the clinical response was
disappointing.
Adverse effects of IV infusion of rHuIL-2 into dogs
include vomiting, diarrhea and lethargy. Adjunct IL-2
gene therapy has been performed in the dog by intratumoral
injection of an IL-2 gene transfected cell line, or
adenoviral vector containing IL-2 cDNA. Although
these procedures show clinical promise, there is a range
of reported side effects.
MISCELLANEOUS AGENTS REPORTED TO
HAVE IMMUNOSTIMULATORY ACTIVITY
Regressin-V
Regressin-V is a mixture of components derived from
the cell wall of Mycobacterium that has been used as an
adjunct immune stimulant (given before surgery) in
bitches with mammary neoplasia. The suggested effects
of this agent are to enhance T-cell activation and proinflammatory
cytokine release from macrophages.
Serratia marcescens
An extract of Serratia marcescens has the ability to
induce myelostimulation and to activate macrophages
with release of proinflammatory cytokines. The agent
has been shown to reduce the myelosuppression caused
by administration of doxorubicin to dogs and to enhance
the synthesis of endogenous G-CSF measured several
hours after administration.
Staphage lysate
Clinical applications
Staphage lysate is a bacterin prepared by bacteriophage
lysis of human-origin Staphylococcus aureus. Staphage
lysate has been given as adjunct therapy to dogs with
idiopathic recurrent superficial pyoderma but has not
been extensively evaluated in cases of deep pyoderma.
Treatment has been shown to be beneficial in up to 70%
of cases of superficial pyoderma.
Mechanism of action
The objective of administration is to enhance the host
immune response to Staphylococcus spp; however,
repeated injection of staphage lysate does not lead to
elevated levels of serum antibody specific for S. intermedius
antigens in dogs with superficial pyoderma.
Formulations and dose rates
• One suggested dosage regimen is to administer staphage
lysate, concurrently with appropriate antibiotics, at 0.5 mL twice
weekly for 6 weeks by SC injection. Following cessation of
antibiotics, staphage lysate monotherapy is continued for a
further 4–8 weeks
• In order to maintain remission, intermittent administration of
staphage lysate may be required thereafter
Adverse effects
● Local injection site reactions
● Pyrexia
● Lethargy
● Vomiting
Staphoid AB
Clinical applications
Staphoid AB is a bacterin preparation that contains a
mixture of Staphylococcus aureus cell wall antigen,
together with α- and β-toxins. This agent is marketed
in some countries for the prevention of staphylococcal
mastitis in cows and has been evaluated in canine
pyoderma, but appears less efficacious than staphage
lysate.
Formulations and dose rates
The suggested dosage regimen involves administration of increasing
increments given by a combination of intradermal and SC injection
over a 5-d period (total dose 0.25 mL on day 1, increasing to 1.25 mL
on day 5), then weekly for 3 weeks (increasing from 1.5 to 2.0 mL)
and monthly (2.0 mL doses) thereafter.
284