Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance
The course and outcome of infection with the parasitic protozoa <i>Leishmania major</i> depends on the host immune response which, itself, depends mainly on the cytokine milieu, especially early in the infection. It is widely accepted that INF-γ, TNF-α, and IL-12 usually favor a protecti...
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2024-12-01
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| author | Muriel Tahtouh Zaatar Sara Salman Reem Hoblos Rabih Roufayel Ziad Fajloun Jean-Marc Sabatier Marc Karam |
| author_facet | Muriel Tahtouh Zaatar Sara Salman Reem Hoblos Rabih Roufayel Ziad Fajloun Jean-Marc Sabatier Marc Karam |
| author_sort | Muriel Tahtouh Zaatar |
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| description | The course and outcome of infection with the parasitic protozoa <i>Leishmania major</i> depends on the host immune response which, itself, depends mainly on the cytokine milieu, especially early in the infection. It is widely accepted that INF-γ, TNF-α, and IL-12 usually favor a protective response, while IL-4, IL-5, IL-10, and IL-13 favor a pathogenic one. These and other cytokines also play a major role in <i>Leishmania</i>-induced hyperalgesia via two possible pathways, one involving prostaglandins and the other sympathetic amines as final mediators, preceded by a cascade of cytokines, among which TNF-α seems to play a pivotal role via a still unclear mechanism of action. This study investigates the effects of anti-TNF-α antibody (Infliximab) on <i>L. major</i>-induced hyperalgesia in susceptible BALB/c mice using the hot plate and tail flicks tests, as well as the levels of many cytokines in the infected paws of mice using the ELISA technique. In addition, the parasite burden was assessed using the serial dilution method. Our results show that Infliximab can reduce the induced hyperalgesia, up-regulate TNF-α, IL-1β, and keratinocyte-derived chemokine (KC), and down-regulate IL-10 and IL-17 in the paws of infected mice. Infliximab may also have beneficial effects on the prognosis of cutaneous leishmaniasis by reducing the parasite burden. |
| format | Article |
| id | doaj-art-02b7d3610bc1419ab7c09737d456da37 |
| institution | Kabale University |
| issn | 2036-7481 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-02b7d3610bc1419ab7c09737d456da372025-01-24T13:41:43ZengMDPI AGMicrobiology Research2036-74812024-12-01161810.3390/microbiolres16010008Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite ClearanceMuriel Tahtouh Zaatar0Sara Salman1Reem Hoblos2Rabih Roufayel3Ziad Fajloun4Jean-Marc Sabatier5Marc Karam6Biological and Physical Sciences Department, American University in Dubai, Dubai P.O. Box 28282, United Arab EmiratesBiology Department, Faculty of Sciences, University of Balamand, Al-Kourah, Tripoli P.O. Box 100, LebanonBiology Department, Faculty of Sciences, University of Balamand, Al-Kourah, Tripoli P.O. Box 100, LebanonCollege of Engineering and Technology, American University of the Middle East, Egaila 54200, KuwaitDepartment of Cell Culture, Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, Doctoral School of Sciences and Technology, Lebanese University, Tripoli 1300, LebanonAix-Marseille Université, CNRS, INP, Inst Neurophysiopathol, 13385 Marseille, FranceBiology Department, Faculty of Sciences, University of Balamand, Al-Kourah, Tripoli P.O. Box 100, LebanonThe course and outcome of infection with the parasitic protozoa <i>Leishmania major</i> depends on the host immune response which, itself, depends mainly on the cytokine milieu, especially early in the infection. It is widely accepted that INF-γ, TNF-α, and IL-12 usually favor a protective response, while IL-4, IL-5, IL-10, and IL-13 favor a pathogenic one. These and other cytokines also play a major role in <i>Leishmania</i>-induced hyperalgesia via two possible pathways, one involving prostaglandins and the other sympathetic amines as final mediators, preceded by a cascade of cytokines, among which TNF-α seems to play a pivotal role via a still unclear mechanism of action. This study investigates the effects of anti-TNF-α antibody (Infliximab) on <i>L. major</i>-induced hyperalgesia in susceptible BALB/c mice using the hot plate and tail flicks tests, as well as the levels of many cytokines in the infected paws of mice using the ELISA technique. In addition, the parasite burden was assessed using the serial dilution method. Our results show that Infliximab can reduce the induced hyperalgesia, up-regulate TNF-α, IL-1β, and keratinocyte-derived chemokine (KC), and down-regulate IL-10 and IL-17 in the paws of infected mice. Infliximab may also have beneficial effects on the prognosis of cutaneous leishmaniasis by reducing the parasite burden.https://www.mdpi.com/2036-7481/16/1/8parasitic protozoa<i>Leishmania major</i>immunomodulationcytokineTNF-αhyperalgesia |
| spellingShingle | Muriel Tahtouh Zaatar Sara Salman Reem Hoblos Rabih Roufayel Ziad Fajloun Jean-Marc Sabatier Marc Karam Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance Microbiology Research parasitic protozoa <i>Leishmania major</i> immunomodulation cytokine TNF-α hyperalgesia |
| title | Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance |
| title_full | Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance |
| title_fullStr | Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance |
| title_full_unstemmed | Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance |
| title_short | Blocking TNF-α Reduces <i>Leishmania major</i>-Induced Hyperalgesia and Changes the Cytokine Profile in the Paw Skin of BALB/c Mice with a Potential Positive Effect on Parasite Clearance |
| title_sort | blocking tnf α reduces i leishmania major i induced hyperalgesia and changes the cytokine profile in the paw skin of balb c mice with a potential positive effect on parasite clearance |
| topic | parasitic protozoa <i>Leishmania major</i> immunomodulation cytokine TNF-α hyperalgesia |
| url | https://www.mdpi.com/2036-7481/16/1/8 |
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