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As part of the cellular [[stress response]], [[superoxide]] is one of the major [[reactive oxygen species]] induced by LPS in various cell types that express TLR ([[toll-like receptor]]).<ref>{{cite journal | vauthors = Li Y, Deng SL, Lian ZX, Yu K | title = Roles of Toll-Like Receptors in Nitroxidative Stress in Mammals | journal = Cells | volume = 8 | issue = 6 | page = 576 | date = June 2019 | pmid = 31212769 | pmc = 6627996 | doi = 10.3390/cells8060576 | doi-access = free }}</ref> LPS is also an exogenous [[Pyrogen (fever)|pyrogen]] (fever-inducing substance).<ref name="Roth_2014" />
LPS function has been under experimental research for several years due to its role in activating many [[transcription factor]]s. LPS also produces many types of mediators involved in [[septic shock]]. Of mammals, humans are much more sensitive to LPS than other primates<ref>{{cite journal | vauthors = Brinkworth JF, Valizadegan N.| display-authors = 2 | title = Sepsis and the evolution of human increased sensitivity to lipopolysaccharide.| journal = Evol Anthropol.| volume = 30 | issue = 2 | pages = 141-157| date = 2021 | pmid = 33689211 | doi = 10.1002/evan.21887. | }}</ref>, and other animals as well (e.g., mice). A dose of 1 μg/kg induces shock in humans, but mice will tolerate a dose up to a thousand times higher.<ref>{{cite journal | vauthors = Warren HS, Fitting C, Hoff E, Adib-Conquy M, Beasley-Topliffe L, Tesini B, Liang X, Valentine C, Hellman J, Hayden D, Cavaillon JM | display-authors = 6 | title = Resilience to bacterial infection: difference between species could be due to proteins in serum | journal = The Journal of Infectious Diseases | volume = 201 | issue = 2 | pages = 223–232 | date = January 2010 | pmid = 20001600 | pmc = 2798011 | doi = 10.1086/649557 }}</ref> This may relate to differences in the level of circulating natural antibodies between the two species.<ref>{{cite journal | vauthors = Reid RR, Prodeus AP, Khan W, Hsu T, Rosen FS, Carroll MC | title = Endotoxin shock in antibody-deficient mice: unraveling the role of natural antibody and complement in the clearance of lipopolysaccharide | journal = Journal of Immunology | volume = 159 | issue = 2 | pages = 970–975 | date = July 1997 | pmid = 9218618 | doi = 10.4049/jimmunol.159.2.970 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Boes M, Prodeus AP, Schmidt T, Carroll MC, Chen J | title = A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection | journal = The Journal of Experimental Medicine | volume = 188 | issue = 12 | pages = 2381–2386 | date = December 1998 | pmid = 9858525 | pmc = 2212438 | doi = 10.1084/jem.188.12.2381 }}</ref> It may also be linked to linked to multiple immune tactics against pathogens, and part of a multi-faceted anti-microbial strategy that has been informed by human behavioral changes over our species' evolution (e.g., meat eating, agricultural practices, and smoking)<ref name="Brinkworth_2021" />. Said et al. showed that LPS causes an [[Interleukin 10|IL-10]]-dependent inhibition of [[CD4 T-cell]] expansion and function by up-regulating [[PD-1]] levels on [[monocytes]] which leads to IL-10 production by monocytes after binding of PD-1 by [[PD-L1]].<ref>{{cite journal | vauthors = Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, Hill BJ, Noto A, Ancuta P, Peretz Y, Fonseca SG, Van Grevenynghe J, Boulassel MR, Bruneau J, Shoukry NH, Routy JP, Douek DC, Haddad EK, Sekaly RP | display-authors = 6 | title = Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection | journal = Nature Medicine | volume = 16 | issue = 4 | pages = 452–459 | date = April 2010 | pmid = 20208540 | pmc = 4229134 | doi = 10.1038/nm.2106 }}</ref>
Endotoxins are in large part responsible for the dramatic clinical manifestations of infections with pathogenic Gram-negative bacteria, such as ''[[Neisseria meningitidis]]'', the pathogens that causes [[meningococcal disease]], including [[meningococcemia]], [[Waterhouse–Friderichsen syndrome]], and [[meningitis]].
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