[Transforming growth factor beta, metalloproteinase 2 and its tissue inhibitor 2 in the serum from patients with early and late boreliosis].
Boreliosis is an arthropod transmitted, bacterial infection, known for its complicated pathogenesis and prolonged course. Boreliosis can be divided into early, localized type, early generalized type as well as late type. Cytokines control homeostasis of the organism by transmitting signals between cells. TGF (transforming growth factor) beta is one of the cytokines that modulates cell differentiation, proliferation and angiogenesis. In larger concentrations it blocks the expression of IL-1 and TNF-alfa. TGF-beta stimulates production of selectin, collagen, fibrinoectin and integrin. It inhibits metalloproteinase that causes degradation of the above mentioned proteins.


OBJECTIVE
We assessed a concentration of TGF-beta in the blood of patients presented with an early form of boreliosis Erythema Migrans (EM) as well as in patients with an advanced form of this disease Lyme arthritis (LA) In addition, levels of metalloproteinase (MMP-2), its tissue inhibitor (TIMP) was assessed. We attempted to analyze the effects of treatment by measuring specific markers of inflammation.


METHODS
We tested a group of 40 patients with Lyme disease. The first group included 20 patients with an early form--(EM), while the second group of 20 patients, had a chronic form of the disease--(LA). The control group consisted of 8 healthy blood donors. The serum levels of TGF beta, metalloproteinase (MMP-2) and its tissue inhibitor (TIMP-2) were obtained using ELISA. Levels were obtained prior to treatment and after 4 weeks of treatment with Doxycyclin or Rocephin (Ceftriaxon).


RESULTS
The results indicated that levels of TGF-beta were lower in the Lyme patients than in the healthy control. In the patients group, the early form of disease had higher levels of TGF-beta than in the chronic. Acute, early phase group had also higher serum levels of MMP-2 and TIMP-2 in comparison to the chronic stage group. LA group showed correlation between TGF-beta concentration and levels of MMP-2. It has not been the case in the acute stage of the disease. Both groups of patients had higher levels of IL-1-aRII and selectin E in comparison with control.


CONCLUSIONS
As suggested by the results, decreased levels of TGF-beta in patients with boreliosis can be due to increased levels of MMP-2 and TIMP. The above markers and their concentration can be useful in the monitoring of the effectiveness of provided therapy and suggest that inflammation can persist in spite of the normalization of the clinical picture. The results suggest extremely complicated pathophysiology of Lyme disease where pro and antiinflammatory cytokines are as important as the pathogen itself.
Pancewicz
Sławomir A
SA
Uniwersytet Medyczny w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji. neuroin@amb.edu.pl
Izycka
Aneta
A
Klibingat
Marcin
M
Zajkowska
Joanna M
JM
Swierzbińska-Pijanowska
Renata
R
Kondrusik
Maciej
M
Grygorczuk
Sambor S
SS
Izycki
Tomasz
T
Hermanowska-Szpakowicz
Teresa
T
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008193:Lyme Disease / Q000097:blood*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood*
D015415:Biomarkers; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2