Cytokines in Lyme borreliosis: lack of early tumour necrosis factor‐α and transforming growth factor‐β₁ responses are associated with chronic neuroborreliosis

Abstract

Summary The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor‐α (TNF‐α), transforming growth factor β1 (TGF‐β1) and interleukin‐6 (IL‐6) in samples drawn at different disease intervals during the course of non‐chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF‐α were found in non‐chronic patients than in chronic patients (P<0·05). Moreover, TGF‐β1 was increased in the early serum samples of non‐chronic patients, as compared to chronic patients (P<0·01). Elevated serum levels of TGF‐β1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0·05). The high TNF‐α levels noted in early cerebrospinal fluid samples of non‐chronic patients only, possibly reflects an ongoing pro‐inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF‐β1 probably mirror an anti‐inflammatory response, which might play a role in controlling the systemic immune response.

Diagnostic Value of Cytokines and Chemokines in Lyme Neuroborreliosis

“…High concentrations of interleukin 6 (IL-6), IL-8, IL-12, IL-18, gamma interferon (IFN-␥), and CXCL13 have been found in the CSF samples of patients suffering from Lyme neuroborreliosis (7)(8)(9)(10)(11). Interleukin 6 induces the final maturation of B cells into plasma cells, IL-8 is a chemotactic factor for immune cells, IL-12 induces the Th1 response, which results in a strong inflammatory reaction caused by IFN-␥ and tumor necrosis factor beta (TNF-␤), and IL-18 is an important regulator of the immune response, which in synergy with IL-12 increases the secretion of IFN-␥ (7,8).…”

Interleukin-10 Anti-Inflammatory Response toBorrelia burgdorferi, the Agent of Lyme Disease: a Possible Role for Suppressors of Cytokine Signaling 1 and 3

“…Spirochetal persistence in the tissues has been associated with severe pathology (14,21,65) and both acute and chronic inflammatory conditions (50,59). Numerous studies have shown that B. burgdorferi and its lipoproteins can induce in a variety of cell types the release of proinflammatory cytokines, such as interleukin-1␣ (IL-1␣) (10), IL-1␤ (45), 23,45,54,55,64), IL-8 (10), IL-12 (30,45,58), tumor necrosis factor alpha (TNF-␣) (8,45,53,54,55,58,64), gamma interferon (IFN-␥) (22,23,24), IL-17 (35), granulocyte-macrophage colony-stimulating factor (GM-CSF) (67), and IL-18 (30). These cytokines may contribute to tissue inflammation and damage.…”

Mechanisms of Immune and Cytokine Regulation in Pathogenesis of Ixodes Tick-Borne Borreliosis

“…В последние годы имеет место повышенный ин-терес к изучению функций цитокинов в формировании и регуляции защитно-приспособительных реакций орга-низма при инфекционных процессах [4][5][6]. Начальные фазы иммунного ответа на боррелиозную инфекцию протекают с высвобождением провоспалительных ци-токинов.…”

“…Начальные фазы иммунного ответа на боррелиозную инфекцию протекают с высвобождением провоспалительных ци-токинов. Фазность цитокиновой регуляции проявляется закономерным компенсаторным увеличением продукции противовоспалительных цитокинов, способствующих купированию воспалительных процессов [4,7]. Актив-ность синтеза цитокинов, экспрессии рецепторов к ним на клетках-мишенях определяют характер течения за-болевания [6,7].…”

“…Ряд исследований свидетельству-ет о преобладании T х2 (гуморального) типа иммунного ответа при остром течении заболевания [8][9][10][11]. В то же время существуют доказательства значимого участия в иммунопатогенезе T х1 (клеточного) типа иммунного от-вета, в результате которого происходит непосредственное стимулирующее действие на фагоцитоз и цитотоксиче-ские лимфоциты [4,[12][13][14].…”