Lyme Neuroborreliosis: Evidence for Persistent Up‐Regulation of <i>Borrelia Burgdorferi</i>‐Reactive Cells Secreting Interferon‐γ

Wang, W.-Z.; Fredrikson, Sten; Sun, Jiabin; Link, Hans

doi:10.1111/j.1365-3083.1995.tb03713.x

Cited by 26 publications

(22 citation statements)

References 30 publications

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“…Interestingly, in paired samples of serum and CSF, levels of IL‐6 were significantly higher in the CSF than in serum ( P <0·001), suggesting that the IL‐6 production is intrathecal, and compartmentalized to the CNS. Similar findings of compartmentalization of immune responses in borreliosis have previously been reported 14,15 , 32 . One reason for finding lower IL‐6 levels in CSF from patients with Lyme borreliosis compared to controls could be that IL‐6 is in fact increased in our controls.…”

Section: Discussionsupporting

confidence: 89%

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

Widhe

Grusell²,

Ekerfelt

et al. 2002

Immunology

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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.

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Section: Discussionsupporting

confidence: 89%

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

Widhe

Grusell²,

Ekerfelt

et al. 2002

Immunology

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“…Furthermore, early treatment with recombinant IL-4 cured the susceptible animals [10]. Th1-like responses in human borreliosis have been reported by us and others [12][13][14][15]. Th1-like responses in human borreliosis have been reported by us and others [12][13][14][15].…”

Section: Introductionmentioning

confidence: 98%

AsymptomaticBorrelia-seropositive individuals display the same incidence ofBorrelia-specific interferon-gamma (IFN-γ)-secreting cells in blood as patients with clinicalBorreliainfection

Ekerfelt

Forsberg

Svenvik

et al. 1999

Clinical and Experimental Immunology

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Borrelia Lyme disease is a complex disorder that sometimes becomes chronic. There are contradictory reports of experimental Borrelia infections regarding which type of T cell cytokine responses, i.e. Th1 or Th2, are needed to eradicate the Borrelia spirochaetes. In human borreliosis a predominance of Borrelia-specific Th1-like responses has been shown. In this study, spontaneous, as well as Borrelia-specific, secretion of IFN-gamma (Th1) and IL-4 (Th2) in Borrelia-seropositive healthy asymptomatic individuals (n = 17) was investigated in peripheral blood by a sensitive ELISPOT assay, and compared with previously reported responses in patients with clinical Borrelia infection (n = 25). The seropositive asymptomatic individuals displayed the same predominance of Borrelia-specific IFN-gamma-secreting cells as the patients with clinical Borrelia infection. Interestingly, the proportion of spontaneously IL-4-secreting cells, reflecting the unstimulated in vivo secretion, was lower in the seropositive asymptomatic individuals compared with patients with chronic Borrelia infections (n = 13, P = 0.02), whereas no such difference was found compared with subacute Borrelia infections (n = 12). These findings indicate that IFN-gamma secretion alone is not sufficient to eliminate Borrelia spirochaetes in humans, although IFN-gamma may still have a beneficial role in borreliosis acting in concert with other mechanisms.

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“…a weak initial inflammatory response, not generating proper down-regulatory feedback mechanisms. Indeed, previous investigations in both mice [16], [17] and humans [18]–[21] have indicated that a successful clinical outcome requires an effective inflammatory T helper cell (Th) 1-type response that is adequately balanced by an anti-inflammatory and Th2-like response against B. burgdorferi .…”

Section: Introductionmentioning

confidence: 99%

Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

et al. 2011

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BackgroundDespite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e.g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome.MethodsA prospective follow-up study of 109 patients with EM was conducted at the Åland Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-γ, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines.FindingsNone of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-γ in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels.ConclusionPatients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.

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Lyme Neuroborreliosis: Evidence for Persistent Up‐Regulation of Borrelia Burgdorferi‐Reactive Cells Secreting Interferon‐γ

Cited by 26 publications

References 30 publications

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

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

AsymptomaticBorrelia-seropositive individuals display the same incidence ofBorrelia-specific interferon-gamma (IFN-γ)-secreting cells in blood as patients with clinicalBorreliainfection

Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

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Lyme Neuroborreliosis: Evidence for Persistent Up‐Regulation of Borrelia Burgdorferi‐Reactive Cells Secreting Interferon‐γ

Cited by 26 publications

References 30 publications

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

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

AsymptomaticBorrelia-seropositive individuals display the same incidence ofBorrelia-specific interferon-gamma (IFN-γ)-secreting cells in blood as patients with clinicalBorreliainfection

Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

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

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