TY  - JOUR
A1  - Schapovalova, Olesia
A1  - Gorlova, Anna
A1  - de Munter, Johannes
A1  - Sheveleva, Elisaveta
A1  - Eropkin, Mikhail
A1  - Gorbunov, Nikita
A1  - Sicker, Michail
A1  - Umriukhin, Aleksei
A1  - Lyubchyk, Sergiy
A1  - Lesch, Klaus-Peter
A1  - Strekalova, Tatyana
A1  - Schroeter, Careen A.
T1  - Immunomodulatory effects of new phytotherapy on human macrophages and TLR4- and TLR7/8-mediated viral-like inflammation in mice
JF  - Frontiers in Medicine
N2  - Background
While all efforts have been undertaken to propagate the vaccination and develop remedies against SARS-CoV-2, no satisfactory management of this infection is available yet. Moreover, poor availability of any preventive and treatment measures of SARS-CoV-2 in economically disadvantageous communities aggravates the course of the pandemic. Here, we studied a new immunomodulatory phytotherapy (IP), an extract of blackberry, chamomile, garlic, cloves, and elderberry as a potential low-cost solution for these problems given the reported efficacy of herbal medicine during the previous SARS virus outbreak.


Methods
The key feature of SARS-CoV-2 infection, excessive inflammation, was studied in in vitro and in vivo assays under the application of the IP. First, changes in tumor-necrosis factor (TNF) and lnteurleukin-1 beta (IL-1β) concentrations were measured in a culture of human macrophages following the lipopolysaccharide (LPS) challenge and treatment with IP or prednisolone. Second, chronically IP-pre-treated CD-1 mice received an agonist of Toll-like receptors (TLR)-7/8 resiquimod and were examined for lung and spleen expression of pro-inflammatory cytokines and blood formula. Finally, chronically IP-pre-treated mice challenged with LPS injection were studied for “sickness” behavior. Additionally, the IP was analyzed using high-potency-liquid chromatography (HPLC)-high-resolution-mass-spectrometry (HRMS).


Results
LPS-induced in vitro release of TNF and IL-1β was reduced by both treatments. The IP-treated mice displayed blunted over-expression of SAA-2, ACE-2, CXCL1, and CXCL10 and decreased changes in blood formula in response to an injection with resiquimod. The IP-treated mice injected with LPS showed normalized locomotion, anxiety, and exploration behaviors but not abnormal forced swimming. Isoquercitrin, choline, leucine, chlorogenic acid, and other constituents were identified by HPLC-HRMS and likely underlie the IP immunomodulatory effects.


Conclusions
Herbal IP-therapy decreases inflammation and, partly, “sickness behavior,” suggesting its potency to combat SARS-CoV-2 infection first of all via its preventive effects.
KW  - toll-like receptors
KW  - SARS-CoV-2
KW  - inflammation
KW  - pro-inflammatory cytokines
KW  - mice
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286301
SN  - 2296-858X
VL  - 9
ER  - 
TY  - JOUR
A1  - Kühlhorn, Franziska
A1  - Rath, Matthias
A1  - Schmoeckel, Katrin
A1  - Cziupka, Katharina
A1  - Nguyen, Huu Hung
A1  - Hildebrandt, Petra
A1  - Hünig, Thomas
A1  - Sparwasser, Tim
A1  - Huehn, Jochen
A1  - Pötschke, Christian
A1  - Bröker, Barbara M.
T1  - \(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis
JF  - PLoS ONE
N2  - The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
KW  - CD4(+)CD25(+)
KW  - toll-like receptors
KW  - TGF-BETA
KW  - mediated suppression
KW  - polymicrobial sepsis
KW  - improves survival
KW  - adoptive transfer
KW  - infected mice
KW  - in-vivo
KW  - CD4(+)
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130940
VL  - 8
IS  - 5
ER  -