LTCI is a safe, effective treatment aid.
As a naturally-occurring, immune-modulating protein, LTCI is the first USDA-approved treatment aid for osteoarthritis in dogs.
LTCI & Dogs
Canine OA can be treated with LTCI
The long prevailing understanding of osteoarthritis (OA) has been that of an age-related degenerative disease caused by “wear and tear”, in contrast to the immune mediated cause of rheumatoid arthritis (RA). However, over more than a decade, numerous studies have demonstrated that lymphocyte subset abnormalities in OA are identical to those observed in RA1, suggesting a similar immunological etiology for both joint related diseases. It has also been demonstrated that synovial fluid from OA and RA patients contain the same abnormal CD-4 lymphocyte subsets with memory/activated markers, e.g. CD45RO2. Furthermore, it has been reported that dogs with synovial stifle and cranial cruciate ligament rupture have an increase in CD-4 lymphocytes in the joint, which correlates with radiographic evidence of OA3.
Most recently it has been observed that LTCI is a true immunomodulator by virtue of its mechanism of action, i.e. increasing the number and function of precursors (CD4+CD45RA+CD62L+) of a regulatory T-Cell population. Thus, it can increase immune responses to foreign antigens and dampen immune-mediated responses to self-antigens. Based upon that observation, and the demonstration that OA is caused by chronic immune activation against joint tissue, a double-blind placebo controlled study in 24 dogs with OA was conducted. The average improvement in limb function in 11 of 12 LTCI treated dogs was 40%+ based upon the “gold standard”, objective force plate analysis. In contrast, the placebo group had an average -17% decrease in function. Based upon the results, USDA's Center for Veterinary Biologics granted conditional approval of LTCI's use as an aid to treat osteoarthritis in dogs one year or older. LTCI, now provides a safe, well-tolerated alternative to nonsteroidal anti-inflammatory drugs (NSAIDS) which can be problematic, especially in older dogs, when mobility is severely compromised.
Recommended Canine OA Treatment Schedule
Upon diagnosis of Canine OA:
- Administer an initial 3 doses in weeks 1 and 2 and 2 doses in weeks 3 and 4.
- Subsequent injections may be given as necessary monthly or bi-monthly based upon blood results and symptoms.
A veterinarian should decide the best treatment schedule based upon a dog's symptoms, condition and history. Just as every patient presents individually, each one will respond differently to LTCI—some patients may require more frequent treatments.
Administration
1 ml dosage (1μg/ml) by subcutaneous injection.
Contraindications
There are no known contraindications for use of Lymphocyte T-Cell Immunomodulator.
Patient Monitoring
The most important monitoring method is clinical improvement. Quality of life is a critical aspect of clinical improvement. Each patient should be monitored for clinical signs associated with their mobility.
When LTCI is used as an aid in treating OA, observe clinical mobility and if there is lymphocytosis, counts should return to normal within 4 weeks.
1 Leheita O, Abed Elrazek NY, Younes S, et al. Lymphocytes subsets in osteoarthritis versus rheumatoid arthritis. [Journal Article] Egypt J Immunol 2005; 12(2):113-24
2 Hisakata Yamada, Yasuharu Nakashima, Ken Okazaki, et. al., Preferential Accumulation of Activated Th1 Cells Not Only in Rheumatoid Arthritis but Also in Osteoarthritis Joints. J Rheumatol August 2011 38(8):1569-1575;
3 Peter Muir BVSc, MVetClinStud, PhD, Diplomate ACVS, Jennifer L. Kelly DVM. Sarah Jane Marvel DVM, et.al., Lymphocyte Populations in Joint Tissues from Dogs with Inflammatory Stifle Arthritis and Associated Degenerative Cranial Cruciate Ligament Rupture. Veterinary Surgery, Volume 40, Issue 6, pages 753–761, August 2011
How Does LTCI Work?
LTCI is a naturally-occurring, immune-modulating protein that helps restore homeostasis. For dogs with OA, it improves mobility by reducing lymphocytosis and dampening the immune-mediated disease process within the joint(s) and progressive joint degeneration.
The result is normalization of blood parameters and resolution of symptoms. LTCI aids in the treatment of OA by restoring normal immune function in your pets.
Safety First
Clients depend on safe products for their pets' well-being. Veterinarians demand safe products for treating ill patients. LTCI has completed formal safety testing. The homology of LTCI among mammalian species, as well as the absence of any observed adverse events in several animal species, demonstrates that LTCI is well tolerated.
PLEASE NOTE: LTCI is restricted to use by or under the supervision of a veterinarian. Veterinarians may order by calling (800) 483-2104 ext. 87 or setting up an online account. Cat owners should contact their veterinarian about ordering or locate a vet already using LTCI.
The Science Behind the Product
Discovery and Characterization
Prior to 1960, the thymus gland was thought to be of little importance. In adult animals, the thymus is almost nonexistent because it atrophies as animals reach adulthood. It was observed, however, that when pre-adolescent animals are thymectomized, they experience a variety of maladies including increased incidence of infection, failure to grow, neuromuscular disorders, cancer, etc.— collectively known as “wasting disease”. The greater susceptibility to infection was shown to be directly attributable to a dramatic decrease in peripheral blood lymphocytes in thymectomized animals.
By 1964 it had been demonstrated that regulatory factors extracted from the thymus gland could prevent many of the manifestations of wasting disease. This suggested that the thymus produces substances important in the development of immunity. It was not until 1971 that it was discovered that thymus-derived lymphocytes (T-cells) were important regulators of bone-marrow-derived antibody-producing lymphocytes (B-cells). After the discovery that the thymus was producing profound regulatory factors, several groups of scientists began trying to extract and purify these factors from thymus glands in much the same manner that insulin was prepared from the pancreas for therapeutic use in diabetes. The difficulty was that the thymus is a very small gland and produces very small quantities of these factors. Thus, purification techniques did not allow appropriate pure fractions to be produced in sufficient quantities.
In 1983 scientists succeeded in cloning epithelial cell lines from the thymus of various species and began to biochemically and biologically characterize these thymus derived regulatory factors. A protein with a molecular weight of about 50,000 daltons was subsequently described and shown to modulate the immune response. This protein was assigned the true name Lymphocyte T-Cell Immunomodulator (LTCI) by the USDA.
Biological Properties
Normally a proportion of immature thymus-derived lymphocytes differentiate into mature CD-4+ T-cells which produce a number of cytokines, including interleukin-2 (IL-2) and gamma interferon. CD-4 cells coordinate the overall immune response and help activate CD-8 T-lymphocytes, which attack viruses and tumor cells. CD-8+ T-lymphocytes are often called “effector” or “cytotoxic” T-cells, because they respond to intracellular pathogens and cancer cells. Under viral attack, CD-4+ T-cells fail to mature, fail to produce IL-2 and gamma interferon, and consequently fail to coordinate CD-8 responses to viruses. Because LTCI increases the production of CD-4+ T-cells, this immunosuppression can be overcome by treatment.
Because of its action on CD4+ T-cells, LTCI also promotes hematopoiesis. It is now well established that CD4+ T-cells regulate the production of all blood cell types in the bone marrow, including red blood cells, platelets, and granulocytes. A deficiency in CD-4+ T-cells thus leads to the anemia observed in immunocompromised subjects including cancer patients undergoing chemotherapy, or viral or other chemically induced conditions.
In summary, the primary action of LTCI is directed toward the production and activation of mature T-lymphocytes, resulting in increased production of IL-2 and interferon in physiological amounts and ratios. These cytokines stimulate a cascade of events that enhance or potentiate both cell mediated immunity as well as antibody-mediated responses.
Biochemical Properties
Lymphocyte T-Cell Immunomodulator is a single chain polypeptide. It is a strongly cationic glycoprotein, and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection.