Effects of low dose radiation therapy on adjuvant induced arthritis in rats.
OBJECTIVE
Substantial clinical evidence shows the efficacy of low dose radiotherapy (RT) in the treatment of painful osteoarthritis. Experimental investigations into these empirically clinical observations remain scarce. This study investigated in vivo the effects of daily 5 x 1.0 Gy versus 5 x 0.5 Gy on adjuvant induced arthritis in rats in order to explore whether there is a dose dependence of anti-inflammatory efficacy.


METHODS
Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat inactivated Mycobacterium tuberculosis on day 0. Both hind paws were X-irradiated daily from days 15 to 19 after induction according to four protocols (15 animals/group): group 1, 5 x 1.0 Gy (non-arthritic animals); group 2, sham-irradiated control; group 3, 5 x 1.0 Gy; group 4, 5 x 0.5 Gy. The clinical parameters arthritis score (AS), hind paw volume (HPV), body weight, and erythrocyte sedimentation rate (ESR) were determined. On days 21 and 30 histological sections of at least 12 ankle joints per group were analysed semi-quantitatively.


RESULTS
Local irradiation of non-arthritic rats (group 1) with 5 x 1 Gy did not induce any arthritic signs. Sham-irradiated arthritic rats (group 2) showed a full-blown arthritic syndrome. Treatment of arthritic rats with 5 x 1 Gy (group 3) or 5 x 0.5 Gy (group 4) led to a reduction of mean AS from day 21 to 29 compared with group 2 (days 27-29--group 3: p=0.037; group 4: p=0.034), with no differences in efficacy between groups 3 and 4. Concurrently, following radiation treatment there was no further increase in HPV. At the end of the observation period, this effect demonstrated a dose-dependent level of significance (days 27-29--group 3: p=0.0036; group 4: p=0.039). A significant decrease in the ESR was noted in both irradiated arthritic groups on day 21 (group 3: p=0.015; group 4: p=0.006). The histopathological analysis revealed a highly significant reduction of cartilage and bone destruction on day 30 in both irradiated groups.


CONCLUSIONS
This study confirms by objective criteria the anti-inflammatory efficacy of low dose RT and gives some indication for a dose dependence of its efficacy.
Hildebrandt
G
G
Department of Radiotherapy and Radiooncology, University of Leipzig, Germany. hilg@server3.medizin.uni-leipzig.de
Jahns
J
J
Hindemith
M
M
Spranger
S
S
Sack
U
U
Kinne
R W
RW
Madaj-Sterba
P
P
Wolf
U
U
Kamprad
F
F
D000818:Animals; D001169:Arthritis, Experimental / Q000382:microbiology / Q000503:physiopathology / Q000532:radiotherapy*; D005260:Female; D009169:Mycobacterium tuberculosis; D011879:Radiotherapy Dosage; D051381:Rats; D011917:Rats, Inbred Lew