text: Imiquimod (cardinally used in dermatology) is a TLR7 agonist, and its successor resiquimod, is a TLR7 and TLR8 agonist. Recently, resiquimod has been explored as an agent for cancer immunotherapy, acting through stimulation of tumor-associated macrophages.
  Several TLR ligands are in clinical development or being tested in animal models as vaccine adjuvants, with the first clinical use in humans in a recombinant herpes zoster vaccine in 2017, which contains a monophosphoryl lipid A component.
  TLR7 messenger RNA expression levels in dairy animals in a natural outbreak of foot-and-mouth disease have been reported.
  TLR4 has been shown to be important for the long-term side-effects of opioids. Its activation leads to downstream release of inflammatory modulators including TNF-α and IL-1β, and constant low-level release of these modulators is thought to reduce the efficacy of opioid drug treatment with time, and is involved in opioid tolerance, hyperalgesia and allodynia. Morphine induced TLR4 activation attenuates pain suppression by opioids and enhances the development of opioid tolerance and addiction, drug abuse, and other negative side effects such as respiratory depression and hyperalgesia. Drugs that block the action of TNF-α or IL-1β have been shown to increase the analgesic effects of opioids and reduce the development of tolerance and other side-effects, and this has also been demonstrated with drugs that block TLR4 itself.
  The "unnatural" enantiomers of opioid drugs such as (+)-morphine and (+)-naloxone lack affinity for opioid receptors, still produce the same activity at TLR4 as their "normal" enantiomers. So, "unnatural" entianomers of opioids such as (+)-naloxone, can be used to block the TLR4 activity of opioid analgesic drugs without having any affinity for μ-opioid receptor