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Abstract
This study aimed to analyze the anti-inflammatory effects of tetracyclines in rheumatoid arthritis patients focusing on their immunomodulatory effects, in consideration for future therapeutic prospects.
It included twenty Egyptian active rheumatoid arthritis patients diagnosed according to the proposed American collage of rheumatology revised criteria (ACR) (1987) for the classification of rheumatoid arthritis. The patients did not take any of the following drugs for at least three months before the study (disease modifying anti-rheumatic drugs ”DMARDs”, corticosteroids and systemic antibiotic therapy). Three weeks wash out from non-steroidal anti-inflammatory drugs ”NSAIDs” were allowed for each patient.
All the patients received doxycycline (semisynthetic tetracycline) 100 mg twice daily and were allowed to receive a pain killer drug eg: paracetamol and codeine derivatives.
All selected patients were subjected to: personal data, full medical history, and evaluation:
I. Clinically [baseline (day 0) and every 28 days]:
A- Evaluation using disease activity score (DAS 28).
B- Evaluation of improvement of the disease by WHO ”World Health Organization”/ILAR ”International League Against Rheumatism” response criteria.
C- Evaluation of the side effects of the treatment with doxycycline.
II. Laboratory evaluation (blood evaluation at baseline and after 6 months of the therapy.
1- C-reactive protein (CRP).
2- Rheumatoid factor (RF) by Latex, Rose Waaler tests.
3- Metalloproteinase-3 level (MP3).
4- Interleukin-1 level (IL1).
5- Demonstration of T-lymphocytes apoptosis.
III. Radiological evaluation (base line and after 6 months of therapy) of wrists, hands and forefeet according to the criteria of kellgren.
After six months of treatment protocol with oral doxycycline there was moderate improvement of the disease according to DAS activity and DAS improvement with statistical significance before and after the treatment period. There was negative correlation between DAS activity and DAS improvement ie: when the activity was high the improvement was low.
The same moderate improvement was found by WHO/ILAR score with statistical significance before and after the treatment period.
In our study there were 9 cases from 20 who had previous urinary tract infections 2-4 weeks mean duration before they became rheumatoid arthritis patients and this supports the theory that rheumatoid arthritis is a form of reactive arthritis.
Regarding the side effects from doxycycline treatment in our study there were only 3 patients had GIT side effects in the form of maldigestion and fullness, the remaining 17 patients didn’t develop any side effects of doxycycline neither dizziness, rash, headache, skin and mucosal hyperpigmentation, lupus like syndrome, nor liver affection who was confirmed by liver function tests before and after treatment.
As doxycycline down regulate the inflammatory process in chronic inflammatory diseases associated with local infiltration of inflammatory cells, we studied the level of interleukin-1 (IL-1) before doxycycline and we found decrease in their level after treatment, with significant difference.
In our study we measured the level of MMP-3 before and after 6 months of doxycycline treatment and we found decrease in their levels after treatment with significant difference.
Also, we measured apoptosis of T-cell in the serum of rheumatoid arthritis patients using flowcytometer apparatus before and after 6 months of treatment and we found significant increase in T-cell apoptosis after doxycycline treatment which is a good sign of reduced disease activity with treatment.
Regarding the radiological changes of the wrists, hands and forefeet of our cases using kellgren radiology score, we found that there were no changes in the radiological finding during these 6 months of treatment which may be a good sign of positive effect of oral doxycycline in reducing the activity of inflammation in our rheumatoid arthritis patients.