Kr. Knight et al., AUTOLOGOUS LYMPHOCYTE THERAPY FOR EXPERIMENTAL CANINE LYMPHEDEMA - A PILOT-STUDY, Australian and New Zealand journal of surgery, 64(5), 1994, pp. 332-337
Obstructive lymphoedema, an accumulation of protein-rich fluid in inte
rstitial spaces, was created in five dogs by a combination of the irra
diation of one groin and subsequent surgical ablation of any remaining
lymphatics. The lymphoedema was stable for up to 2 years. The aim was
to test the efficacy of intra-arterial injection of autologous lympho
cytes as a therapy for lymphoedema. The hypothesis was that cytokines
produced by lymphocytes mediate proteolysis by macrophage proteinases
in the lymphoedematous limb to remove the excess protein and relieve t
he oedema. A concentrated lymphocyte-rich preparation was isolated fro
m blood by the Ficoll-Paque method. These preparations were injected i
nto the femoral artery four times at approximately 4 weekly intervals.
Three months after the first injection of lymphocytes, lymphoedematou
s limbs showed a marked 69% reduction in the mean excess circumference
s compared with opposite control limbs. After treatment, skin thicknes
s and hydroxyproline content (both measures of fibrosis) as well as wa
ter content (a measure of oedema) had reduced significantly. In specim
ens of interstitial fluid and in skin homogenates acidic proteinase ac
tivity increased and the protein concentration decreased significantly
compared with controls. It is concluded that increased proteolysis, p
ossibly due to activated macrophages recruited to the lymphoedematous
limb, may partly explain these results.