In patients with CIDs, TNF and IL-6 neutralizing strategies reduced IR [ 20, 44, 45].
Furthermore, when cytokine neutralizing strategies do not work in T2D patients, several factors in parallel are expected to drive IR.
Neutralizing strategies for HMGB1 inhibition including 'A-box' or anti-HMGB1 antibody treatment, have successfully reduced mortality in mice with polymicrobial sepsis.
Until now it is not clear why the neutralizing strategies perfectly improve insulin sensitivity in CIDs but not in patients without CIDs.
With the identification of the GBS hemolysin as a lipid, understanding how the toxin itself contributes to inflammation, cytotoxicity, and preterm birth is critical for development of neutralizing strategies against the lipid toxin.
On the other hand, it is worth mentioning that the combined targeting of the caspase-1 downstream targets, IL-1 β and IL-18 by using their knockout mice or neutralizing strategies using the IL-1 β receptor antagonist, anakinra and anti-IL-18 antibodies, conferred complete protection against endotoxin-induced lethality.
Due to redundant pathways in stimulating IR, a simple one factor-neutralizing strategy might help in chronic inflammatory diseases (inflammation is the key), but not in obesity-related IR.
Our results also encourage to screen csU patients for IgE directed against autoantigens other than TPO and to test IgE-neutralizing strategies such as omlizumab for their efficacy in csU.
In chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin sensitivity.
When cytokine-neutralizing strategies do not work in obese or T2D people, other parallel factors must play an enormous role.
