Investigation of recombinant human insulin-like growth factor type I in thymus regeneration in the acute stage of experimental FIV infection in juvenile cats
Jc. Woo et al., Investigation of recombinant human insulin-like growth factor type I in thymus regeneration in the acute stage of experimental FIV infection in juvenile cats, AIDS RES H, 15(15), 1999, pp. 1377-1388
Thymus involvement and the development of thymic lesions in HIV-1 infection
is hypothesized to suppress thymus function and limit T cell maturation an
d replenishment of the peripheral lymphoid pool. Therapeutic modulation to
protect or enhance thymus function may therefore ameliorate peripheral lymp
hocytopenia and retard disease progression. Thymotrophic agents, such as in
sulin-like growth factor type I (IGF-I), may therefore represent adjunctive
but important methods of treatment to protect or promote thymus function.
The assessment of rhIGF-I in lentiviral infection and its impact on the thy
mus was performed using the feline immunodeficiency virus (FIV) model. Rege
neration of the thymus in juvenile cats and amelioration of the thymic lesi
on after FIV infection was assessed by multiple measurements including thym
ic weight, stereologic analysis of the thymus cortex and medulla, histologi
c and immunohistologic analysis, quantitation of thymocyte and peripheral l
ymphocyte subsets, and quantitative competitive RT-PCR, Evidence of thymic
cortical regeneration was observed in FIV-inoculated cats after 12 and 20 w
eeks of rhIGF-I treatment, Inflammation in the thymus was reduced during th
is period of treatment in this group of rhIGF-I/FIV-inoculated cats as evid
enced by the reduced numbers of B cells detected. Viral replication rates i
n peripheral lymph nodes were not altered by rhIGF-I treatment and were dec
reased by 1 log in the thymus after 20 weeks of treatment. Peripheral blood
CD4(+) T cell counts also increased after 14 weeks of treatment. This sugg
ests that rhIGF-I treatment can enhance thymus function and replenishment o
f the peripheral T cell pool.